Bone-marrow-derived mesenchymal stem cells and endothelial progenitor cells have some interesting biological properties that make them unique for cell therapy of degenerative and cardiovascular disorders.Although both...Bone-marrow-derived mesenchymal stem cells and endothelial progenitor cells have some interesting biological properties that make them unique for cell therapy of degenerative and cardiovascular disorders.Although both cell populations have been already studied and used for their regenerative potentials,recently their special immunoregulatory features have brought much more attention.Mesenchymal stem cells and endothelial progenitor cells have both proangiogenic functions and have been shown to suppress the immune response,particularly T cell proliferation,activation,and cytokine production.This makes them suitable choices for allogeneic stem cell transplantation.Nevertheless,these two cells do not have equal immunoregulatory activities.Many elements including their extraction sources,age/passage,expression of different markers,secretion of bioactive mediators,and some others could change the efficiency of their immunosuppressive function.However,to our knowledge,no publication has yet compared mesenchymal stem cells and endothelial progenitor cells for their immunological interaction with T cells.This review aims to specifically compare the immunoregulatory effect of these two populations including their T cell suppression,deactivation,cytokine production,and regulatory T cells induction capacities.Moreover,it evaluates the implications of the tumor necrosis factor alpha-tumor necrosis factor receptor 2 axis as an emerging immune checkpoint signaling pathway controlling most of their immunological properties.展开更多
In this article, we invertigated changes of immune functions and immunoregulatory effects of indomethacin on rats with trauma. The results show that spontaneous suppressor T cell activity of spleen significantly incre...In this article, we invertigated changes of immune functions and immunoregulatory effects of indomethacin on rats with trauma. The results show that spontaneous suppressor T cell activity of spleen significantly increased and Interleukin 2 production and DNA synthesis capacity of splenocytes markedly decreased in rats with trauma. Indomethacin could markedly improve immune function , decreased spontancous suppressor T cell activity and prompted Interleukin 2 production and DNA synthesis capacity of splenocytes.展开更多
The immunoregulatory effect of TLSFJM on the expression of T cell IL- 2R and protein tyrosine phosphorylation ( PTP ) was investigated by immunohistochemistry technique. The results showed that TLSFJMcan markedly supp...The immunoregulatory effect of TLSFJM on the expression of T cell IL- 2R and protein tyrosine phosphorylation ( PTP ) was investigated by immunohistochemistry technique. The results showed that TLSFJMcan markedly suppress the expression of IL-2R and PTP on PHA or TPA-stimulated human PBMC and murine IL-2 dependent cell line CTLL-2. However, there was no effect of TLSFJMon the production of IL-1, IL-2 and IL-6 that play an important role in the course of T lymphocyte proliferation and differentiation.展开更多
Based on the researches on immunoregulatory functions of Dendrobium. at home and abroad in recent years,from immune organs,immune cells,and immune molecules,this paper summarized immunoregulatory functions of polysacc...Based on the researches on immunoregulatory functions of Dendrobium. at home and abroad in recent years,from immune organs,immune cells,and immune molecules,this paper summarized immunoregulatory functions of polysaccharides,glycosides,and alkaloids extracted from Dendrobium. on the body,including reducing the inflammation,inhibiting tumor,and slowing down aging,to provide theoretical references for in-depth researches and development of modern biotechnology for Dendrobium.展开更多
A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy.Here,a new type of spatiotemporal bio...A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy.Here,a new type of spatiotemporal biomimetic“Gemini nanoimmunoregulators”was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death(ICD),tumor-associated macrophages(TAMs)phenotype reprogramming and programmed cell death ligand 1(PD-L1)degradation.The“Gemini nanoimmunoregulators”PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine(mPDA)as nanovectors to deliver metformin(Met)and toll-like receptor 7/8 agonist resiquimod(R848)to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane(RM)inlaid with T7or M2 peptides.mPDA/Met@RM-T7(abbreviated as PM@RM-T7)was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity.Meanwhile,PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion.Subsequently,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recognized TAMs and reset the phenotype from M2 to M1 state,thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes.This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity,which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis.This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.展开更多
Tripterygium wilfordii Hook F (TwHF) and its extracts have long been used for the treatment of rheumatoid arthritis, autoimmune diseases, and kidney disease due to their anti-inflammatory, immunoregulatory, and other ...Tripterygium wilfordii Hook F (TwHF) and its extracts have long been used for the treatment of rheumatoid arthritis, autoimmune diseases, and kidney disease due to their anti-inflammatory, immunoregulatory, and other pharmacological effects. However, the clinical immunoregulatory effects of TwHF and its extracts remain unclear, so we reviewed their effects for use in clinical practice. This review provides a comprehensive summary of the recent literature on the immunoregulatory effects of TwHF and its extracts in clinical studies. TwHF and its extracts affect the proliferation and activation of T and B cells;ratio of T cell subsets;inflammatory response of monocytes, macrophages, and immunoglobulins;and secretion of many cytokines. Together, these effects dictate immune function in a variety of diseases. TwHF and its extracts can be used alone or in combination with existing therapies against many immune disorders through immunomodulation.展开更多
Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) tha...Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents. In vitro experiments demonstrated that the proinflammatory solvent ethanol stabilized the hydrogel structure, maintained the phenolic hydroxyl group activity, and achieved macrophages' proinflammatory transition (M0 to M1) to enhance antibacterial effects. With ethanol depletion, the hydrogel's cations and phenolic hydroxyl groups synergistically regulated macrophages' anti-inflammatory transition (M1 to M2) to initiate regeneration. In the anti-contraction full-thickness wound model with infection, this hydrogel effectively eliminated bacteria and even achieved anti-inflammatory M2 macrophage accumulation at three days post-surgery, accelerated angiogenesis and collagen deposition. By sequentially driving macrophage phenotypic polarization, this injectable immunoregulatory hydrogel will bring new guidance for the care and treatment of infected wounds.展开更多
SOCS8,also known as CISHb,is a fish-specific type Ⅱ SOCS.Because CISH binds to cytokine receptors and may inhibit STAT5 activation(a substrate of the insulin receptor),SOCS8 may be involved in the control of metaflam...SOCS8,also known as CISHb,is a fish-specific type Ⅱ SOCS.Because CISH binds to cytokine receptors and may inhibit STAT5 activation(a substrate of the insulin receptor),SOCS8 may be involved in the control of metaflammation.The socs8-/-zebrafish were created,and both longer trunks and intestinal villi were observed in 1-month-old(mo)fish.Altered mucosal immunity and gut-liver metabolism were also found in socs8-/-fish.Increased intestinal neutrophils and macrophages,together with overexpression of cytokines and T cell markers in this mutant fish,suggested SOCS8's immunoregulating role.During modeling of soybean-induced enteritis using the 3 mo zebrafish,lower expression levels of inflammatory genes but more mucosa barrier disruption were discovered in socs8-/-zebrafish,compared with wide type counterparts.Furthermore,the shrunk villi at 6 mo in socs8-/-fish suggested that the mucosa might have been protected by SOCS8.This is also consistent with the assertion that metaflammation eventually leads to tissue degeneration and premature death.The fact that socs8-/-fish had more hepatic oil droplets compared to their wild-type counterparts suggested SOCS8's role in inhibiting hepatic metaflammation.Transcriptomic analysis as well as 16S rRNA gene sequencing were done on 3 mo socs8-/-fish to methodically reveal the altered immunity and metabolic reprogramming in the gut and liver caused by socs8-/-.The enriched GO terms for the intestinal tract,such as"cytokine-mediated signaling pathway"and"response to external biotic stimulus",as well as KEGG pathways in both gut and liver like"carbon metabolism"and"glycolysis/gluconeogenesis",were consistent with previously revealed pathological clues and improved growth performance at early age,respectively.In addition,the microbiota in the socs8-/-strain had adapted to the host's increased carbohydrate metabolism,as evidenced by higher levels of Bacteroidota.Furthermore,Verrucomicrobiota associated with immunoregulation were found in lower abundance in socs8-/-fish.As a result,current findings indicate that SOCS8 plays immunoregulatory and mucosa-protective roles in the fish gut and liver by inhibiting carbohydrate metabolism.展开更多
The healing of diabetic wounds poses a significant healthcare burden due to persistent inflammation,M1 macrophage aggregation,and high glucose levels in the microenvironment.Previous studies have demonstrated that imm...The healing of diabetic wounds poses a significant healthcare burden due to persistent inflammation,M1 macrophage aggregation,and high glucose levels in the microenvironment.Previous studies have demonstrated that immunomodulatory hydrogel dressings can facilitate diabetic wound healing.However,current immunomodulatory hydrogels require costly and complex treatments such as cell therapy and cytokines.Herein,a hierarchical hydrogel dressing with continuous biochemical gradient based on glycyrrhizic acid(GA) was constructed to modulate immunomodulatory processes in diabetic wounds.The hydrogels present many desirable features,such as tunable mechanical properties,broad antibacterial ability,outstanding conductive,transparent,and self-adhesive properties.The resultant hydrogel can promote diabetic wound healing by preventing bacterial infection,promoting macrophage polarization,improving the inflammatory microenvironment,and inducing angiogenesis and neurogenesis.Furthermore,electrical stimulation(ES) can further promote the healing of chronic diabetic wounds,providing valuable guidance for relevant clinical practice.展开更多
Diabetes mellitus(DM)is a serious health problem in the world,and infections are common complications in diabetic patients,particularly methicillin-resistant Staphylococcus aureus(MRSA)infections,which substantially i...Diabetes mellitus(DM)is a serious health problem in the world,and infections are common complications in diabetic patients,particularly methicillin-resistant Staphylococcus aureus(MRSA)infections,which substantially increases mortality in patients.In clinical practice,the treatment of diabetic complicationrelated infections involves multiple issues such as drug resistance when combining antidiabetic drugs with antibiotics.In this study,a series of derivatives were synthesized with alkyl radicals with different chain lengths substituted at the C8 and C12 positions of berberine,with compounds CY1 and CY3with good antidiabetic and antibacterial activities screened out after identification.Then,oral liposomes(CY1-Lip and CY3-Lip)were prepared,and their particle sizes,stability,and pharmacokinetics were investigated.In acquired mouse models of diabetes,induced with an acute MRSA lung infection,we demonstrate that CY1-Lip and CY3-Lip can effectively reduce levels of fasting blood glucose(FBG),fasting insulin(FINS),and insulin resistance index among diabetic mice with pneumonia,thus exerting their multitargets effects.Furthermore,both preparations significantly reduced lung MRSA loads and improved lung tissue lesions,reduced high infiltration of M1 macrophages in lung,and suppressed the expression levels of pro-infiammatory factors such as necrosis factor-α(TNF-α)and interleukin-6(IL-6).This provides new insights into the clinical treatment of diabetes complicated with pulmonary infections.展开更多
Lupus nephritis(LN)is one of the most common and serious complications of systemic lupus erythematosus,which can lead to end-stage renal disease,and is an important cause of death in patients with systemic lupus eryth...Lupus nephritis(LN)is one of the most common and serious complications of systemic lupus erythematosus,which can lead to end-stage renal disease,and is an important cause of death in patients with systemic lupus erythematosus.Treatment options include glucocorticoids,immunosuppressive agents and the addition of biologics.Recently,the therapeutic role of mesenchymal stem cells(MSCs)in LN has received extensive attention worldwide.MSCs can suppress autoimmunity,alleviate proteinuria and restore renal function by modulating the functions of various immune cells and reducing the secretion of inflammatory cytokines.Several clinical trials have investigated MSC treatment in LN with promising but sometimes inconsistent outcomes.This review summarizes the sources of MSCs and mechanisms in immunoregulation.Furthermore,it examines clinical trials evaluating the efficacy,safety,and limitations of MSC therapy in LN.By highlighting advances and ongoing challenges,this review underscores the potential of MSCs for LN treatment.More large-scale randomized controlled trials are needed to support the effectiveness of this therapy and pave the way for personalized and combinatorial therapeutic approaches.展开更多
Materials and Methods: lymphocytes of 10 pa-tients having early rheumatoid arthritis (RA) (the duration of the illness was 3 - 6 months) with a marked exudational process in joints were ex-amined. The content of lymph...Materials and Methods: lymphocytes of 10 pa-tients having early rheumatoid arthritis (RA) (the duration of the illness was 3 - 6 months) with a marked exudational process in joints were ex-amined. The content of lymphocytes expressing the CD3, CD4, CD8, CD16, CD56, CD20, CD72, CD38, CD23, CD25, CD71, HLA-DR, CD95, CD30, CD54, mIgM, mIgG antigens was determined. Results: the “Taban-Arshan” extract corrects the changes of the immune system characterized by the evident activation of the B-cell part of the immune system and normalizes immune parameters of the lymphocytes taken from the patients with autoimmune diseases (early rheumatoid arthritis). The immunocorrective effect of the “Taban-Arshan” extract is related to its ability to suppress the lymphocyte increased activation by normalizing expression of the main activation antigens (CD23, CD25, CD71, HLA-DR, CD54).展开更多
Strong evidence supports the concept of immunosurveillance and immunoediting in colorectal cancer. In particular, the density of T CD8<sup>+</sup> and CD45<sup>+</sup> lymphocyte infiltration w...Strong evidence supports the concept of immunosurveillance and immunoediting in colorectal cancer. In particular, the density of T CD8<sup>+</sup> and CD45<sup>+</sup> lymphocyte infiltration was recently shown to have a better prognostic value than the classic tumor node metastasis classification factor. Other immune subsets, as macrophages, natural killer cells or unconventionnal lymphocytes, seem to play an important role. Induction of regulatory T cells (Tregs) or immunosuppressive molecules such as PD-1 or CTLA-4 and downregulation of antigen-presenting molecules are major escape mechanisms to antitumor immune response. The development of these mechanisms is a major obstacle to the establishment of an effective immune response, but also to the use of immunotherapy. Although immunotherapy is not yet routinely used in colorectal cancer, we now know that most treatments used (chemotherapy and biotherapy) have immunomodulatory effects, such as induction of immunogenic cell death by chemotherapy, inhibition of immunosuppression by antiangiogenic agents, and antibody-dependent cytotoxicity induced by cetuximab. Finally, many immunotherapy strategies are being developed and tested in phase I to III clinical trials. The most promising strategies are boosting the immune system with cytokines, inhibition of immunoregulatory checkpoints, vaccination with vectorized antigens, and adoptive cell therapy. Comprehension of antitumor immune response and combination of the different approaches of immunotherapy may allow the use of effective immunotherapy for treatment of colorectal cancer in the near future.展开更多
In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial i...In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial invasion, which induces an inflammatory process to localize the infection and prevent systemic dissemination of pathogens. The key elements of this process are the germline encoded pattern recognition receptors including Toll-like receptors (TLRs). If pathogens cannot be eliminated, they may elicit chronic inflammation, which may be partly mediated via TLRs. Additionally, chronic inflammation has long been suggested to trigger tissue tumorous transformation. Inflammation, the seventh hallmark of cancer, may affect all phases of tumor development, and evade the immune system. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability. Furthermore, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Colorectal cancers in inflammatory bowel disease patients are considered typical examples of inflammation-related cancers. Although data regarding the role of TLRs in the pathomechanism of cancer-associated colitis are rather conflicting, functionally these molecules can be classified as ”largely antitumorigenic” and ”largely pro-tumorigenic” with the caveat that the underlying signaling pathways are mainly context (i.e., organ-, tissue-, cell-) and ligand-dependent.展开更多
The pathogenesis and outcome of viral infections are significantly influenced by the host immune response. The immune system is able to eliminate many viruses in the acute phase of infection. However, some viruses, li...The pathogenesis and outcome of viral infections are significantly influenced by the host immune response. The immune system is able to eliminate many viruses in the acute phase of infection. However, some viruses, like hepatitis C virus (HCV) and hepatitis B virus (HBV), can evade the host immune responses and establish a persistent infection. HCV and HBV persistence is caused by various mechanisms, like subversion of innate immune responses by viral factors, the emergence of T cell escape mutations, or T cell dysfunction and suppression. Recently, it has become evident that regulatory T cells may contribute to the pathogenesis and outcome of viral infections by suppressing antiviral immune responses. Indeed, the control of HCV and HBV specific immune responses mediated by regulatory T cells may be one mechanism that favors viral persistence, but it may also prevent the host from overwhelming T cell activity and liver damage. This review will focus on the role of regulatory T cells in viral hepatitis.展开更多
Summary： Although mesenchymal stem cells （MSCs） are increasingly used to treat graft-versus-host disease （GVHD）, their immune regulatory mechanism in the process is elusive. The present study aimed to investigate...Summary： Although mesenchymal stem cells （MSCs） are increasingly used to treat graft-versus-host disease （GVHD）, their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs （UCB-hMSCs） on GVHD patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT） and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK ceils, Treg cells and dendritic cells （DCs） and cytokines including interleukin-17 （IL-17） and tumor necrosis factor-alpha （TNF-α） were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3^＋, CD3＋CD4^＋ and CD3＋CD8^＋ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4^＋ and CD8^＋ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.展开更多
Acupuncture is an effective therapy used worldwide to treat various diseases,including infections,allergic disorders,autoimmune diseases,and immunodeficiency syndromes.Except for the hypothalamic-pituitary-adrenal axi...Acupuncture is an effective therapy used worldwide to treat various diseases,including infections,allergic disorders,autoimmune diseases,and immunodeficiency syndromes.Except for the hypothalamic-pituitary-adrenal axis,acupuncture exerts its regulatory effect mainly by producing autonomic reflexes,including somatic-sympathetic and somatic-parasympathetic reflexes.In this review,we discuss the updated progress of the cholinergic vagal efferent pathway,vagal-adrenal axis,local spinal sacral-parasympathetic pathway,and the somatotopic evocation of parasympathetic responses related to restoring immune homeostasis within acupuncture therapy.Targeting the parasympathetic reflex offers scientific instruction for the design of acupuncture protocols for immunological diseases,providing more specialized comprehensive treatment recommendations.展开更多
AIM： To study the immunoregulatory effect of 1,25-dihydroxyvitamin-D3 Von dominant Thl response in rats. METHODS： Sixty adult Lewis rats were randomized into three groups. Rats in group 1 （n=25） were treated with ...AIM： To study the immunoregulatory effect of 1,25-dihydroxyvitamin-D3 Von dominant Thl response in rats. METHODS： Sixty adult Lewis rats were randomized into three groups. Rats in group 1 （n=25） were treated with 1,25-（OH）2D3 first and then challenged with LPS, rats in group 2 （n=25） were treated with vehicle first and then challenged with LPS. Ten animals in groups 1 and 2 were preserved for mortality observation. The remaining animals were injected （i.p） with endotoxin, 24 h after the last administration of 1,25-（OH）2D3 and vehicle. Rats in group 3 （n=10） were treated with 1,25-（OH）2D3 only. Serum IL-12, IFN-y, IL-2 and IL-4 levels were measured and target gene of 1,25-（OH）2D3 on Th cells was studied after 6 h. Gene abundance was verified by real-time quantitative PCR. RESULTS： No death occurred in rats pretreated with 1,25-（OH）2D3 after LPS injection. Death occurred 9 h after LPS injection in rats pretreated with the vehicle, and the number of deaths was 5 within 24 h, with a mortality rate of 50%. There was no change in the number of deaths within 96 h. Six hours after endotoxin stimulation, serum IL-12 and IFN-y levels decreased significantly in rats pretreated with 1,25-（OH）2D3 as compared with those in rats pretreated with the vehicle. The serum content of these two cytokines was very low in rats not challenged by endotoxin, and there was a significant difference as compared with the previous two groups. CONCLUSION： 1,25-（OH）2D3 attenuates injuryinduced by the lethal dose of 1PS, regulates Thl and Th2 cells at the transcription level, and dominantly responds to cytokine production in rats.展开更多
Mesenchymal stem cells （MSCs） are multipotent stem cells capable of differentiating into various cell types,including osteocytes,chondrocytes,adipocytes,myocytes,and tenocytes.However,the difficulty or failure in ex...Mesenchymal stem cells （MSCs） are multipotent stem cells capable of differentiating into various cell types,including osteocytes,chondrocytes,adipocytes,myocytes,and tenocytes.However,the difficulty or failure in expanding the mouse MSCs in vitro greatly hampered important research in animal models.The OP9,a stromal cell line from mouse bone marrow,has hematopoietic supportive capacity.Here,we report that the OP9 has the immunophenotype （CD45-,CD11b-,FLK-1-,CD31-,CD34-,CD44＋,CD29＋,Sca-1＋,CD86-,and MHCII-） identical to canonical mouse MSCs.The expression of CD140a＋,CD140b＋,α-SMA＋ and Calponin＋ suggested the perivascular origin of OP9.Functionally,the OP9 had strong clonogenic ability and could be induced into osteocytes,chondrocytes and adipocytes.The lymphocyte transformation test （LTT） and mixed leukocyte reaction （MLR） showed that the OP9 could suppress T lymphocyte proliferation stimulated by nonspecific mitogens （PHA） or allogeneic lymphocytes （BALB/c T cells）.Finally,the migration of OP9 could be efficiently induced by bFGF,IGF-1,IL-3,PDGF-BB,TGF-β1 and TGF-β3.In conclusion,the OP9 were bona fide MSCs,and such homogenous cell line will be helpful to delineate biological features of MSCs at the stem cell level.展开更多
Mesenchymal stromal cells (MSCs) are multipotent and self-renewing stem cellsthat have great potential as cell therapy for autoimmune and inflammatorydisorders, as well as for other clinical conditions, due to their i...Mesenchymal stromal cells (MSCs) are multipotent and self-renewing stem cellsthat have great potential as cell therapy for autoimmune and inflammatorydisorders, as well as for other clinical conditions, due to their immunoregulatoryand regenerative properties. MSCs modulate the inflammatory milieu by releasingsoluble factors and acting through cell-to-cell mechanisms. MSCs switch theclassical inflammatory status of monocytes and macrophages towards a nonclassicaland anti-inflammatory phenotype. This is characterized by an increasedsecretion of anti-inflammatory cytokines, a decreased release of pro-inflammatorycytokines, and changes in the expression of cell membrane molecules and inmetabolic pathways. The MSC modulation of monocyte and macrophage phenotypesseems to be critical for therapy effectiveness in several disease models, sincewhen these cells are depleted, no immunoregulatory effects are observed. Here,we review the effects of living MSCs (metabolically active cells) and metabolicallyinactive MSCs (dead cells that lost metabolic activity by induced inactivation) andtheir derivatives (extracellular vesicles, soluble factors, extracts, and microparticles)on the profile of macrophages and monocytes and the implications forimmunoregulatory and reparative processes. This review includes mechanisms ofaction exhibited in these different therapeutic appro-aches, which induce the antiinflammatoryproperties of monocytes and macrophages. Finally, we overviewseveral possibilities of therapeutic applications of these cells and their derivatives,with results regarding monocytes and macrophages in animal model studies andsome clinical trials.展开更多
文摘Bone-marrow-derived mesenchymal stem cells and endothelial progenitor cells have some interesting biological properties that make them unique for cell therapy of degenerative and cardiovascular disorders.Although both cell populations have been already studied and used for their regenerative potentials,recently their special immunoregulatory features have brought much more attention.Mesenchymal stem cells and endothelial progenitor cells have both proangiogenic functions and have been shown to suppress the immune response,particularly T cell proliferation,activation,and cytokine production.This makes them suitable choices for allogeneic stem cell transplantation.Nevertheless,these two cells do not have equal immunoregulatory activities.Many elements including their extraction sources,age/passage,expression of different markers,secretion of bioactive mediators,and some others could change the efficiency of their immunosuppressive function.However,to our knowledge,no publication has yet compared mesenchymal stem cells and endothelial progenitor cells for their immunological interaction with T cells.This review aims to specifically compare the immunoregulatory effect of these two populations including their T cell suppression,deactivation,cytokine production,and regulatory T cells induction capacities.Moreover,it evaluates the implications of the tumor necrosis factor alpha-tumor necrosis factor receptor 2 axis as an emerging immune checkpoint signaling pathway controlling most of their immunological properties.
文摘In this article, we invertigated changes of immune functions and immunoregulatory effects of indomethacin on rats with trauma. The results show that spontaneous suppressor T cell activity of spleen significantly increased and Interleukin 2 production and DNA synthesis capacity of splenocytes markedly decreased in rats with trauma. Indomethacin could markedly improve immune function , decreased spontancous suppressor T cell activity and prompted Interleukin 2 production and DNA synthesis capacity of splenocytes.
文摘The immunoregulatory effect of TLSFJM on the expression of T cell IL- 2R and protein tyrosine phosphorylation ( PTP ) was investigated by immunohistochemistry technique. The results showed that TLSFJMcan markedly suppress the expression of IL-2R and PTP on PHA or TPA-stimulated human PBMC and murine IL-2 dependent cell line CTLL-2. However, there was no effect of TLSFJMon the production of IL-1, IL-2 and IL-6 that play an important role in the course of T lymphocyte proliferation and differentiation.
基金Supported by Special Fund for Basic Scientific Research Project in Chinese Academy of Agricultural Sciences"Research and Demonstration of Key Technology for Processing of Agricultural Products with Tibetan Characteristics"
文摘Based on the researches on immunoregulatory functions of Dendrobium. at home and abroad in recent years,from immune organs,immune cells,and immune molecules,this paper summarized immunoregulatory functions of polysaccharides,glycosides,and alkaloids extracted from Dendrobium. on the body,including reducing the inflammation,inhibiting tumor,and slowing down aging,to provide theoretical references for in-depth researches and development of modern biotechnology for Dendrobium.
基金supported,in part or whole,by the National Natural Science Foundation of China(Nos.32171395,U19A2006,and 12132004)the Sichuan Science and Technology Program(Nos.2021YJ0130,2022NSFSC0048,and 2023NSFSC0715,China)the Joint Funds of Center for Engineering Medicine(Nos.ZYGX2021YGLH010,ZYGX2021YGLH017,and ZYGX2021YGLH204,China)。
文摘A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy.Here,a new type of spatiotemporal biomimetic“Gemini nanoimmunoregulators”was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death(ICD),tumor-associated macrophages(TAMs)phenotype reprogramming and programmed cell death ligand 1(PD-L1)degradation.The“Gemini nanoimmunoregulators”PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine(mPDA)as nanovectors to deliver metformin(Met)and toll-like receptor 7/8 agonist resiquimod(R848)to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane(RM)inlaid with T7or M2 peptides.mPDA/Met@RM-T7(abbreviated as PM@RM-T7)was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity.Meanwhile,PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion.Subsequently,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recognized TAMs and reset the phenotype from M2 to M1 state,thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes.This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity,which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis.This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.
基金the National Natural Science Foundation of China (Nos.81673844, 81573845, 81373773, and 81760838)the Beijing Natural| Science Foundation (No.7142144)+2 种基金China Scholarship Council Fund (No.201609110029)the Interna-tional Cooperation Project of the State Administration of Traditional Chinese Medicine (No.GZYYGJ2017014)the International Cooperation Project of the Ministry of Science and Technology (No.2014DFA31490).
文摘Tripterygium wilfordii Hook F (TwHF) and its extracts have long been used for the treatment of rheumatoid arthritis, autoimmune diseases, and kidney disease due to their anti-inflammatory, immunoregulatory, and other pharmacological effects. However, the clinical immunoregulatory effects of TwHF and its extracts remain unclear, so we reviewed their effects for use in clinical practice. This review provides a comprehensive summary of the recent literature on the immunoregulatory effects of TwHF and its extracts in clinical studies. TwHF and its extracts affect the proliferation and activation of T and B cells;ratio of T cell subsets;inflammatory response of monocytes, macrophages, and immunoglobulins;and secretion of many cytokines. Together, these effects dictate immune function in a variety of diseases. TwHF and its extracts can be used alone or in combination with existing therapies against many immune disorders through immunomodulation.
基金National Key R&D Project of China(No.2022YFC2401800)National Natural Science Foundation of China(32071352 and 32271419).
文摘Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents. In vitro experiments demonstrated that the proinflammatory solvent ethanol stabilized the hydrogel structure, maintained the phenolic hydroxyl group activity, and achieved macrophages' proinflammatory transition (M0 to M1) to enhance antibacterial effects. With ethanol depletion, the hydrogel's cations and phenolic hydroxyl groups synergistically regulated macrophages' anti-inflammatory transition (M1 to M2) to initiate regeneration. In the anti-contraction full-thickness wound model with infection, this hydrogel effectively eliminated bacteria and even achieved anti-inflammatory M2 macrophage accumulation at three days post-surgery, accelerated angiogenesis and collagen deposition. By sequentially driving macrophage phenotypic polarization, this injectable immunoregulatory hydrogel will bring new guidance for the care and treatment of infected wounds.
基金funded by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA24010206)the National Natural Science Fundation of China(31872592).
文摘SOCS8,also known as CISHb,is a fish-specific type Ⅱ SOCS.Because CISH binds to cytokine receptors and may inhibit STAT5 activation(a substrate of the insulin receptor),SOCS8 may be involved in the control of metaflammation.The socs8-/-zebrafish were created,and both longer trunks and intestinal villi were observed in 1-month-old(mo)fish.Altered mucosal immunity and gut-liver metabolism were also found in socs8-/-fish.Increased intestinal neutrophils and macrophages,together with overexpression of cytokines and T cell markers in this mutant fish,suggested SOCS8's immunoregulating role.During modeling of soybean-induced enteritis using the 3 mo zebrafish,lower expression levels of inflammatory genes but more mucosa barrier disruption were discovered in socs8-/-zebrafish,compared with wide type counterparts.Furthermore,the shrunk villi at 6 mo in socs8-/-fish suggested that the mucosa might have been protected by SOCS8.This is also consistent with the assertion that metaflammation eventually leads to tissue degeneration and premature death.The fact that socs8-/-fish had more hepatic oil droplets compared to their wild-type counterparts suggested SOCS8's role in inhibiting hepatic metaflammation.Transcriptomic analysis as well as 16S rRNA gene sequencing were done on 3 mo socs8-/-fish to methodically reveal the altered immunity and metabolic reprogramming in the gut and liver caused by socs8-/-.The enriched GO terms for the intestinal tract,such as"cytokine-mediated signaling pathway"and"response to external biotic stimulus",as well as KEGG pathways in both gut and liver like"carbon metabolism"and"glycolysis/gluconeogenesis",were consistent with previously revealed pathological clues and improved growth performance at early age,respectively.In addition,the microbiota in the socs8-/-strain had adapted to the host's increased carbohydrate metabolism,as evidenced by higher levels of Bacteroidota.Furthermore,Verrucomicrobiota associated with immunoregulation were found in lower abundance in socs8-/-fish.As a result,current findings indicate that SOCS8 plays immunoregulatory and mucosa-protective roles in the fish gut and liver by inhibiting carbohydrate metabolism.
基金supported by Natural Science Foundation of Jilin Province(No.SKL202302002)。
文摘The healing of diabetic wounds poses a significant healthcare burden due to persistent inflammation,M1 macrophage aggregation,and high glucose levels in the microenvironment.Previous studies have demonstrated that immunomodulatory hydrogel dressings can facilitate diabetic wound healing.However,current immunomodulatory hydrogels require costly and complex treatments such as cell therapy and cytokines.Herein,a hierarchical hydrogel dressing with continuous biochemical gradient based on glycyrrhizic acid(GA) was constructed to modulate immunomodulatory processes in diabetic wounds.The hydrogels present many desirable features,such as tunable mechanical properties,broad antibacterial ability,outstanding conductive,transparent,and self-adhesive properties.The resultant hydrogel can promote diabetic wound healing by preventing bacterial infection,promoting macrophage polarization,improving the inflammatory microenvironment,and inducing angiogenesis and neurogenesis.Furthermore,electrical stimulation(ES) can further promote the healing of chronic diabetic wounds,providing valuable guidance for relevant clinical practice.
基金financial support provided by Young Scientists Fund of the National Natural Science Foundation of China(No.32201086)Postdoctoral Science Foundation of Chongqing Natural Science Foundation(No.cstc2021jcyj-bsh X0125)the project for Chongqing University Innovation Research Group,Chongqing Education Committee(No.CXQT20006)。
文摘Diabetes mellitus(DM)is a serious health problem in the world,and infections are common complications in diabetic patients,particularly methicillin-resistant Staphylococcus aureus(MRSA)infections,which substantially increases mortality in patients.In clinical practice,the treatment of diabetic complicationrelated infections involves multiple issues such as drug resistance when combining antidiabetic drugs with antibiotics.In this study,a series of derivatives were synthesized with alkyl radicals with different chain lengths substituted at the C8 and C12 positions of berberine,with compounds CY1 and CY3with good antidiabetic and antibacterial activities screened out after identification.Then,oral liposomes(CY1-Lip and CY3-Lip)were prepared,and their particle sizes,stability,and pharmacokinetics were investigated.In acquired mouse models of diabetes,induced with an acute MRSA lung infection,we demonstrate that CY1-Lip and CY3-Lip can effectively reduce levels of fasting blood glucose(FBG),fasting insulin(FINS),and insulin resistance index among diabetic mice with pneumonia,thus exerting their multitargets effects.Furthermore,both preparations significantly reduced lung MRSA loads and improved lung tissue lesions,reduced high infiltration of M1 macrophages in lung,and suppressed the expression levels of pro-infiammatory factors such as necrosis factor-α(TNF-α)and interleukin-6(IL-6).This provides new insights into the clinical treatment of diabetes complicated with pulmonary infections.
基金Supported by Natural Science Foundation of Zhejiang Province,No.LY23H050005Zhejiang Medical Technology Project,No.2020KY439,No.2022RC009,No.2024KY645,and No.2024KY697.
文摘Lupus nephritis(LN)is one of the most common and serious complications of systemic lupus erythematosus,which can lead to end-stage renal disease,and is an important cause of death in patients with systemic lupus erythematosus.Treatment options include glucocorticoids,immunosuppressive agents and the addition of biologics.Recently,the therapeutic role of mesenchymal stem cells(MSCs)in LN has received extensive attention worldwide.MSCs can suppress autoimmunity,alleviate proteinuria and restore renal function by modulating the functions of various immune cells and reducing the secretion of inflammatory cytokines.Several clinical trials have investigated MSC treatment in LN with promising but sometimes inconsistent outcomes.This review summarizes the sources of MSCs and mechanisms in immunoregulation.Furthermore,it examines clinical trials evaluating the efficacy,safety,and limitations of MSC therapy in LN.By highlighting advances and ongoing challenges,this review underscores the potential of MSCs for LN treatment.More large-scale randomized controlled trials are needed to support the effectiveness of this therapy and pave the way for personalized and combinatorial therapeutic approaches.
文摘Materials and Methods: lymphocytes of 10 pa-tients having early rheumatoid arthritis (RA) (the duration of the illness was 3 - 6 months) with a marked exudational process in joints were ex-amined. The content of lymphocytes expressing the CD3, CD4, CD8, CD16, CD56, CD20, CD72, CD38, CD23, CD25, CD71, HLA-DR, CD95, CD30, CD54, mIgM, mIgG antigens was determined. Results: the “Taban-Arshan” extract corrects the changes of the immune system characterized by the evident activation of the B-cell part of the immune system and normalizes immune parameters of the lymphocytes taken from the patients with autoimmune diseases (early rheumatoid arthritis). The immunocorrective effect of the “Taban-Arshan” extract is related to its ability to suppress the lymphocyte increased activation by normalizing expression of the main activation antigens (CD23, CD25, CD71, HLA-DR, CD54).
文摘Strong evidence supports the concept of immunosurveillance and immunoediting in colorectal cancer. In particular, the density of T CD8<sup>+</sup> and CD45<sup>+</sup> lymphocyte infiltration was recently shown to have a better prognostic value than the classic tumor node metastasis classification factor. Other immune subsets, as macrophages, natural killer cells or unconventionnal lymphocytes, seem to play an important role. Induction of regulatory T cells (Tregs) or immunosuppressive molecules such as PD-1 or CTLA-4 and downregulation of antigen-presenting molecules are major escape mechanisms to antitumor immune response. The development of these mechanisms is a major obstacle to the establishment of an effective immune response, but also to the use of immunotherapy. Although immunotherapy is not yet routinely used in colorectal cancer, we now know that most treatments used (chemotherapy and biotherapy) have immunomodulatory effects, such as induction of immunogenic cell death by chemotherapy, inhibition of immunosuppression by antiangiogenic agents, and antibody-dependent cytotoxicity induced by cetuximab. Finally, many immunotherapy strategies are being developed and tested in phase I to III clinical trials. The most promising strategies are boosting the immune system with cytokines, inhibition of immunoregulatory checkpoints, vaccination with vectorized antigens, and adoptive cell therapy. Comprehension of antitumor immune response and combination of the different approaches of immunotherapy may allow the use of effective immunotherapy for treatment of colorectal cancer in the near future.
文摘In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial invasion, which induces an inflammatory process to localize the infection and prevent systemic dissemination of pathogens. The key elements of this process are the germline encoded pattern recognition receptors including Toll-like receptors (TLRs). If pathogens cannot be eliminated, they may elicit chronic inflammation, which may be partly mediated via TLRs. Additionally, chronic inflammation has long been suggested to trigger tissue tumorous transformation. Inflammation, the seventh hallmark of cancer, may affect all phases of tumor development, and evade the immune system. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability. Furthermore, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Colorectal cancers in inflammatory bowel disease patients are considered typical examples of inflammation-related cancers. Although data regarding the role of TLRs in the pathomechanism of cancer-associated colitis are rather conflicting, functionally these molecules can be classified as ”largely antitumorigenic” and ”largely pro-tumorigenic” with the caveat that the underlying signaling pathways are mainly context (i.e., organ-, tissue-, cell-) and ligand-dependent.
文摘The pathogenesis and outcome of viral infections are significantly influenced by the host immune response. The immune system is able to eliminate many viruses in the acute phase of infection. However, some viruses, like hepatitis C virus (HCV) and hepatitis B virus (HBV), can evade the host immune responses and establish a persistent infection. HCV and HBV persistence is caused by various mechanisms, like subversion of innate immune responses by viral factors, the emergence of T cell escape mutations, or T cell dysfunction and suppression. Recently, it has become evident that regulatory T cells may contribute to the pathogenesis and outcome of viral infections by suppressing antiviral immune responses. Indeed, the control of HCV and HBV specific immune responses mediated by regulatory T cells may be one mechanism that favors viral persistence, but it may also prevent the host from overwhelming T cell activity and liver damage. This review will focus on the role of regulatory T cells in viral hepatitis.
基金supported by grants from the National Natural Science Foundation of China(No.81172826)Collaborative Innovation Center of Hematology,China
文摘Summary： Although mesenchymal stem cells （MSCs） are increasingly used to treat graft-versus-host disease （GVHD）, their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs （UCB-hMSCs） on GVHD patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT） and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK ceils, Treg cells and dendritic cells （DCs） and cytokines including interleukin-17 （IL-17） and tumor necrosis factor-alpha （TNF-α） were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3^＋, CD3＋CD4^＋ and CD3＋CD8^＋ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4^＋ and CD8^＋ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.
基金supported by the National Natural Science Foundation of China(No.82274228)National Key R&D Program of China(No.2022YFC3500700)the Feng Foundation of Biomedical Research,and Lingang Laboratory(No.LG-QS-202203-12).
文摘Acupuncture is an effective therapy used worldwide to treat various diseases,including infections,allergic disorders,autoimmune diseases,and immunodeficiency syndromes.Except for the hypothalamic-pituitary-adrenal axis,acupuncture exerts its regulatory effect mainly by producing autonomic reflexes,including somatic-sympathetic and somatic-parasympathetic reflexes.In this review,we discuss the updated progress of the cholinergic vagal efferent pathway,vagal-adrenal axis,local spinal sacral-parasympathetic pathway,and the somatotopic evocation of parasympathetic responses related to restoring immune homeostasis within acupuncture therapy.Targeting the parasympathetic reflex offers scientific instruction for the design of acupuncture protocols for immunological diseases,providing more specialized comprehensive treatment recommendations.
基金National Basic Research Program of China,2003CB515502
文摘AIM： To study the immunoregulatory effect of 1,25-dihydroxyvitamin-D3 Von dominant Thl response in rats. METHODS： Sixty adult Lewis rats were randomized into three groups. Rats in group 1 （n=25） were treated with 1,25-（OH）2D3 first and then challenged with LPS, rats in group 2 （n=25） were treated with vehicle first and then challenged with LPS. Ten animals in groups 1 and 2 were preserved for mortality observation. The remaining animals were injected （i.p） with endotoxin, 24 h after the last administration of 1,25-（OH）2D3 and vehicle. Rats in group 3 （n=10） were treated with 1,25-（OH）2D3 only. Serum IL-12, IFN-y, IL-2 and IL-4 levels were measured and target gene of 1,25-（OH）2D3 on Th cells was studied after 6 h. Gene abundance was verified by real-time quantitative PCR. RESULTS： No death occurred in rats pretreated with 1,25-（OH）2D3 after LPS injection. Death occurred 9 h after LPS injection in rats pretreated with the vehicle, and the number of deaths was 5 within 24 h, with a mortality rate of 50%. There was no change in the number of deaths within 96 h. Six hours after endotoxin stimulation, serum IL-12 and IFN-y levels decreased significantly in rats pretreated with 1,25-（OH）2D3 as compared with those in rats pretreated with the vehicle. The serum content of these two cytokines was very low in rats not challenged by endotoxin, and there was a significant difference as compared with the previous two groups. CONCLUSION： 1,25-（OH）2D3 attenuates injuryinduced by the lethal dose of 1PS, regulates Thl and Th2 cells at the transcription level, and dominantly responds to cytokine production in rats.
基金supported by the National Natural Science Foundation (Nos 30871410 and 30600613)
文摘Mesenchymal stem cells （MSCs） are multipotent stem cells capable of differentiating into various cell types,including osteocytes,chondrocytes,adipocytes,myocytes,and tenocytes.However,the difficulty or failure in expanding the mouse MSCs in vitro greatly hampered important research in animal models.The OP9,a stromal cell line from mouse bone marrow,has hematopoietic supportive capacity.Here,we report that the OP9 has the immunophenotype （CD45-,CD11b-,FLK-1-,CD31-,CD34-,CD44＋,CD29＋,Sca-1＋,CD86-,and MHCII-） identical to canonical mouse MSCs.The expression of CD140a＋,CD140b＋,α-SMA＋ and Calponin＋ suggested the perivascular origin of OP9.Functionally,the OP9 had strong clonogenic ability and could be induced into osteocytes,chondrocytes and adipocytes.The lymphocyte transformation test （LTT） and mixed leukocyte reaction （MLR） showed that the OP9 could suppress T lymphocyte proliferation stimulated by nonspecific mitogens （PHA） or allogeneic lymphocytes （BALB/c T cells）.Finally,the migration of OP9 could be efficiently induced by bFGF,IGF-1,IL-3,PDGF-BB,TGF-β1 and TGF-β3.In conclusion,the OP9 were bona fide MSCs,and such homogenous cell line will be helpful to delineate biological features of MSCs at the stem cell level.
基金Fundo de IncentivoàPesquisa e Eventos(Fipe)-Hospital de Clínicas de Porto Alegre,No.GPPG 2017-0004.
文摘Mesenchymal stromal cells (MSCs) are multipotent and self-renewing stem cellsthat have great potential as cell therapy for autoimmune and inflammatorydisorders, as well as for other clinical conditions, due to their immunoregulatoryand regenerative properties. MSCs modulate the inflammatory milieu by releasingsoluble factors and acting through cell-to-cell mechanisms. MSCs switch theclassical inflammatory status of monocytes and macrophages towards a nonclassicaland anti-inflammatory phenotype. This is characterized by an increasedsecretion of anti-inflammatory cytokines, a decreased release of pro-inflammatorycytokines, and changes in the expression of cell membrane molecules and inmetabolic pathways. The MSC modulation of monocyte and macrophage phenotypesseems to be critical for therapy effectiveness in several disease models, sincewhen these cells are depleted, no immunoregulatory effects are observed. Here,we review the effects of living MSCs (metabolically active cells) and metabolicallyinactive MSCs (dead cells that lost metabolic activity by induced inactivation) andtheir derivatives (extracellular vesicles, soluble factors, extracts, and microparticles)on the profile of macrophages and monocytes and the implications forimmunoregulatory and reparative processes. This review includes mechanisms ofaction exhibited in these different therapeutic appro-aches, which induce the antiinflammatoryproperties of monocytes and macrophages. Finally, we overviewseveral possibilities of therapeutic applications of these cells and their derivatives,with results regarding monocytes and macrophages in animal model studies andsome clinical trials.
