AIM： To analyze and to compare the effects of interferon （IFN）-α, IFN-β, and IFN-γ on pancreatic stellate cell （PSC） activation/n vitro and to elucidate the molecular basis of IFN action. METHODS： PSCs were i...AIM： To analyze and to compare the effects of interferon （IFN）-α, IFN-β, and IFN-γ on pancreatic stellate cell （PSC） activation/n vitro and to elucidate the molecular basis of IFN action. METHODS： PSCs were isolated from rat＇s pancreatic tissue, cultured and stimulated with recombinant rat IFNs. Cell proliferation and collagen synthesis were assessed by measuring the incorporation of 5-bromo-2＇ -deoxyuridine （BrdU） into DNA and [^3H]-proline into acetic acid-soluble proteins, respectively. Apoptotic ceils were determined by FACS analysis （sub-G1 peak method）. Exhibition of the myofibroblastic PSC phenotype was monitored by immunoblot analysis of （α-smooth muscle actin （α-SMA） expression. To assess the activation of signal transducer and activator of transcription （STAT）, Western blots using phospho- STAT-specific antibodies were performed. In studies on STAT1 function, expression of the protein was inhibited by siRNA. RESULTS： IFN-β and IFN-γ, but not IFN-α significantly diminished PSC proliferation and collagen synthesis. IFN-γ, was the only IFN that clearly inhibited α-SMA expression. Under the experimental conditions used, no enhanced rate of apoptotic cell death was observed in response to any IFN treatment. IFN-β and IFN-γ, induced a strong increase of STAT1 and STAT3 tyrosine phosphorylation, while the effect of IFN-α was much weaker. Inhibition of STAT1 expression with siRNA was associated with a significantly reduced growth-inhibitory effect of IFN-γ. CONCLUSION： IFN-β and particularly IFN-γ, display inhibitory effects on PSC activation in vitro and should be tested regarding their in vitro efficiency. Growth inhibition by IFN-γ action requires STAT1.展开更多
Diabetic retinopathy(DR)is one of the major causes of visual impairment and irreversible blindness in developed regions.Aside from abnormal angiogenesis,inflammation is the most specific and might be the initiating fa...Diabetic retinopathy(DR)is one of the major causes of visual impairment and irreversible blindness in developed regions.Aside from abnormal angiogenesis,inflammation is the most specific and might be the initiating factor of DR.As a key participant in inflammation,interferon-gamma(IFN-γ)can be detected in different parts of the eye and is responsible for the breakdown of the blood-retina barrier and activation of inflammatory cells and other cytokines,which accelerate neovascularization and neuroglial degeneration.In addition,IFN-γis involved in other vascular complications of diabetes mellitus and angiogenesis-dependent diseases,such as diabetic nephropathy,cerebral microbleeds,and age-related macular degeneration.Traditional treatments,such as anti-vascular endothelial growth factor agents,vitrectomy,and laser photocoagulation therapy,are more effective for angiogenesis and not tolerable for every patient.Many ongoing clinical trials are exploring effective drugs that target inflammation.For instance,IFN-αacts against viruses and angiogenesis and is commonly used to treat malignant tumors.Moreover,IFN-αhas been shown to contribute to alleviating the progression of DR and other ocular diseases.In this review,we emphasize the roles that IFNs play in the pathogenesis of DR and discuss potential clinical applications of IFNs in DR,such as diagnosis,prognosis,and therapeutic treatment.展开更多
Hepatitis B virus (HBV) infection is one of the major causes of liver diseases, affecting more than 350 million people worldwide. The interferon (IFN)-mediated innate immune responses could restrict HBV replication at...Hepatitis B virus (HBV) infection is one of the major causes of liver diseases, affecting more than 350 million people worldwide. The interferon (IFN)-mediated innate immune responses could restrict HBV replication at the different steps of viral life cycle. Indeed, IFN-α has been successfully used for treatment of patients with chronic hepatitis B. However, the role of the innate immune response in HBV replication and the mechanism of the anti-HBV effect of IFN-α are not completely explored. In this review, we summarized the currently available knowledge about the IFN-mediated anti-HBV effect in the HBV life cycle and the possible effectors downstream the IFN signaling pathway. The antiviral effect of Toll-like receptors (TLRs) in HBV replication is briefly discussed. The strategies exploited by HBV to evade the IFN- and TLR-mediated antiviral actions are summarized.展开更多
Viruses are obligatory intracellular parasites. Most of the cells in animaland human body possess the innate ability to fight viruses. Innate immune function restrictsinfection at the early stage and delay spread of v...Viruses are obligatory intracellular parasites. Most of the cells in animaland human body possess the innate ability to fight viruses. Innate immune function restrictsinfection at the early stage and delay spread of virus. The early stage of infection is the stage ofinteraction between the virus and the host's defence system. Once the latter is breached, the earlynon-specific or innate immune components such as interferon (IFN), natural killer (NK) cells andmacrophages become active. As the infection proceeds, the adaptive (specific) immune responsedevelops, with the appearance of cytotoxic T cells, helper T cells and antiviral antibodies.Antibodies provide a major barrier to virus spread between cells and cells and are particularlyimportant in restriction of virus spread in the blood stream. Virus infection directly activates thetranscription of type Ⅰ IFN (IFN-alfa/beta) genes in infected cells, while the type Ⅱ IFN(IFN-gamma) plays an essential role in the regulation of an adaptive immune response rather thaninnate immune response. Therefore, Type Ⅰ IFN is the first defence for host and neighbouring cellsto resist virus infection.展开更多
Objective：To investigate the effects and mechanisms of interferon in combination with alltrans retinoic acid （ATRA） on proliferation and differentiation of ATRA-resistent APL cell. Methods ：After MR2 cells （ATRA-...Objective：To investigate the effects and mechanisms of interferon in combination with alltrans retinoic acid （ATRA） on proliferation and differentiation of ATRA-resistent APL cell. Methods ：After MR2 cells （ATRA-resistance cell line） were treated with IFN-α, IFN-γ and ATRA alone or IFN-α and IFN-γ in combination with ATRA respectively. The cell proliferation was tested by MTT test and the cell differentiation was tested through light microscope by NBT test and flow cytometry （FCM）. The expres sion of promyelocytic leukemia （PML） protein was observed by indirect immune fluorescent method. Results： Both IFN-α and IFN-γ could inhibit the proliferation and induce the differentiation of MR2 cells to some extent. The effects were more obvious after both interferons in combination with ATRA respectively （P〈0.05）. Moreover, the maturation of MR2 cells induced by IFN-γ＋ATRA group was more higher than that by IFN-α＋ATRA group （P〈0. 05）. Both interferons could induce the expressions of PML protein. Conclusion：Both interferons can inhibit MR2 cells proliferation, which may be related to the expression of PML protein induced by both interferons. The inducing differentiation effects of IFN-γ＋ATRA group on MR2 cells are more powerful than those of IFN-aq-ATRA group, which may be related to the different signal transduction pathway of both interferons.展开更多
Sjögren’s disease(SjD)is an autoimmune and inflammatory disease characterized by immune-mediated impairment of salivary and lacrimal gland functions,causing dryness in the mouth and eyes.SjD also involves other ...Sjögren’s disease(SjD)is an autoimmune and inflammatory disease characterized by immune-mediated impairment of salivary and lacrimal gland functions,causing dryness in the mouth and eyes.SjD also involves other exocrine glands in the respiratory and gastrointestinal tracts and the skin and has a wide and variable range of extraglandular and systemic manifestations[1].展开更多
Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/s41423-025-01353-z,published online 27 October 2025.The wrong article file was originally published;it has now been replaced with the correct fil...Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/s41423-025-01353-z,published online 27 October 2025.The wrong article file was originally published;it has now been replaced with the correct file.The original article has been corrected.展开更多
A hallmark of systemic lupus erythematosus(SLE)is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies;however,the antibody-independent features of the B-cell compartment in SLE are les...A hallmark of systemic lupus erythematosus(SLE)is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies;however,the antibody-independent features of the B-cell compartment in SLE are less understood.In this study,we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients.We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients.Plasma from SLE patients potently promoted the survival of transitional B cells in a type I IFN-dependent manner,which can be recapitulated by direct IFN-αtreatment.Furthermore,the effect of IFN-αon enhanced survival of transitional B cells was associated with NF-κB pathway activation and reduced expression of the pro-apoptotic molecule Bax.Transitional B cells from SLE patients harbored a higher capacity to produce proinflammatory cytokine IL-6,which was also linked to the overactivated type I IFN pathway.In addition,the frequency of IL-6-producing transitional B cells was positively correlated with disease activity in SLE patients,and these cells were significantly reduced after short-term standard therapies.Thus,the current study provides a direct link between type I IFN pathway overactivation and the abnormally high frequency and proinflammatory properties of transitional B cells in active SLE patients,which contributes to the understanding of the roles of type I IFNs and B cells in the pathogenesis of SLE.展开更多
Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cuta...Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cutaneous vasculopathy,and pulmonary inflammation.We sequenced a candidate gene,TMEM173,encoding the stimulator of interferon genes(STING),in this patient and in five unrelated children with similar clinical phenotypes.Four children were evaluated clinically and immunologically.With the STING ligand cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls,as well as commercially obtained endothelial cells,and then assayed transcription of IFNB1,the gene encoding interferon-β,in the stimulated cells.We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs.Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1(STAT1),so we tested the effect of Janus kinase(JAK)inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls.展开更多
The stimulator of interferon genes(STING),as a critical innate immune sensor,has been widely and continually explored in immune-related disease treatment.As lipid bilayer-closed particles derived from cells,extracellu...The stimulator of interferon genes(STING),as a critical innate immune sensor,has been widely and continually explored in immune-related disease treatment.As lipid bilayer-closed particles derived from cells,extracellular vesicles(EVs)inherently function in target-guided intercellular communication.To incorporate the native merits of EVs into STING pathways,i.e.,engineered EV@STING,poor bioavailability and off-target issues that STING activators possess could be significantly overcome.In this review,emerged STING activators such as nitrogen-containing heterocyclic structures and the universal STING activation strategy(uniSTING)are firstly summarized.Diverse EVs sources from mesenchymal stem cells(MSCs)and innate and adaptive immune cells may evoke distinct regulatory results.Concurrently,how the EVs contents including double-stranded DNA(dsDNA),microRNA(miRNA),cyclic GMP-AMP synthase(cGAS)and 2′3′-cyclic GMP-AMP(2′3′-cGAMP)proteins participate in the regulation of STING activation are widely studied.After mastering the two pivotal aspects of EV@STING,their immunomodulatory roles including in pathogen infection,inflammatory diseases,and cancer therapy are comprehensively summed up and discussed.Finally,in cancer study field,therapeutic challenges and clinical translational opportunities of EV@STING are thoroughly evaluated.展开更多
Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genoty...Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.展开更多
Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cuta...Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cutaneous vasculopathy,and pulmonary inflammation.We sequenced a candidate gene,TMEM173,encoding the stimulator of interferon genes(STING),in this patient and in five unrelated children with similar clinical phenotypes.展开更多
Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever...Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever using interferon type I(IFN-I)or combined IFN-I/II receptor knockout mice infected with dengue virus(DENV).However,this model requires further optimization to better support related studies.Methods:This study aimed to establish a stable dengue infection model by evaluating the effects of different genetic backgrounds and injection routes on DENV infection in interferon receptor knockout mice.We first infected various strains of interferon receptor-deficient mice with DENV and compared their susceptibility based on clini-cal symptoms,viremia levels,organ indices,histopathological findings,and vascular leakage markers.Subsequently,we selected the most susceptible strain to further investigate the impact of different injection methods on infection outcomes.Results:We found that BALB/c background mice with type 1 interferon recep-tor knockout(IFNAR)had the most obvious symptoms.Subsequently,we selected IFNAR−/−BALB/c mice to further explore the effects of different injection methods on dengue virus infection.The results showed that the intraperitoneal injection group had the most severe clinical symptoms,the longest duration of viremia,and the most obvious degree of organ damage.Conclusion:Through systematic screening and optimization,we established a robust animal model of dengue virus infection via intraperitoneal injection in IFNAR−/−BALB/c mice.This model offers a valuable tool for future dengue research.展开更多
Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of a...Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of all the autoimmune rheumatic diseases,SSc has the highest all-cause mortality rate,and the underlying pathogenic processes that mediate disease are still obscure,with wide diff erences in presentation and progression[2,3].展开更多
Purpose To review the efficacy and safety of pegylated interferons (peginterferons) in the treatment of chronic hepatitis C Data sources An English language literature search (MEDLINE 1988-2001) was performed and a...Purpose To review the efficacy and safety of pegylated interferons (peginterferons) in the treatment of chronic hepatitis C Data sources An English language literature search (MEDLINE 1988-2001) was performed and a total of 19 original articles related to the issue were selected Data extraction After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria The papers reviewed pertained mainly to the efficacy and safety profiles of peginterferons in the treatment of chronic hepatitis C Results Peginterferon can effectively prolong the half-life of interferon and can be effectively administered conveniently as a once-a-week dose The antiviral effect using peginterferon was enhanced compared with that of standard interferon, but the frequency and severity of adverse events were typical of those associated with interferon-α Conclusions Based on its efficacy, safety and convenient dosing, peginterferon is more favorable than standard interferon in the treatment of chronic hepatitis C展开更多
The mammalian innate immune system provides the first line of defensive mechanisms to protect the host against invading pathogens.These defensive responses are initiated by recognition of microbial pathogen-associated...The mammalian innate immune system provides the first line of defensive mechanisms to protect the host against invading pathogens.These defensive responses are initiated by recognition of microbial pathogen-associated molecular patterns(PAMPs).展开更多
The major limitation for the maturation of dendritic cells(DCs)using Toll-like receptor(TLR)agonists is their decreased ability to migrate into lymph nodes compared with conventional DCs.CD38 can be used as a multifun...The major limitation for the maturation of dendritic cells(DCs)using Toll-like receptor(TLR)agonists is their decreased ability to migrate into lymph nodes compared with conventional DCs.CD38 can be used as a multifunctional marker to modulate migration,survival and Th1 responses of DCs.CD74 has been shown to negatively regulate DC migration.The goal of this study was to investigate the combinations of TLR agonists and interferons(IFNs)that most effectively regulate CD38 and CD74 expression on DCs.Synergistic TLR agonist stimulation in combination with IFN-a and IFN-c was the best method for regulating CD38 and CD74 expression and inducing the highest secretion of IL-12p70.An in vitro migration assay showed that DCs treated with this combination had significantly enhanced migratory ability,similar to that observed in cells expressing CD38,CD74 and CCR7.The results of this study suggest that an alternative maturation protocol in which two TLR ligands are combined with type I and II IFNs generates potent DCs that have both a high migratory capacity and high IL-12p70 production.展开更多
It is well known that interferons are potential antivirus proteins and possess anticancer capability. In the Thirty-fifth Symposium of the Society for General Microbiology on Interferons held in 1983, Hans Strander re...It is well known that interferons are potential antivirus proteins and possess anticancer capability. In the Thirty-fifth Symposium of the Society for General Microbiology on Interferons held in 1983, Hans Strander reported that interferons had been successfully applied in the treatment of juvenile laryngeal papilloma, papilloma accuminatum, malignant mydomatosis, osteosarcoma, breast cancer, cancer of the colon, non-Hodgkin lymphoma,展开更多
Grass carp hemorrhagic disease caused by grass carp reovirus(GCRV)results in significant economic losses to the global grass carp aquaculture industry.Oral vaccination is an ideal choice for disease precaution in aqua...Grass carp hemorrhagic disease caused by grass carp reovirus(GCRV)results in significant economic losses to the global grass carp aquaculture industry.Oral vaccination is an ideal choice for disease precaution in aquaculture.However,oral vaccine can be degraded in the gut.Therefore,the selection of loading materials is essential.In this study,the S6 and S7 fragments(encoding the outer capsid protein VP4 and fibronectin VP56 of GCRV)and grass carp interferons(IFNs),including IFN1,IFN3,and IFNγ2 were used to create DNA vaccines and adjuvants based on pcDNA3.1,respectively.The oral DNA vaccine was encapsulated in poly(lactic-co-glycolic acid)(PLGA)and polyvinyl alcohol(PVA)with IFNs.The PLGA-PVA(PP)nano-microspheres were prepared by double emulsionsolvent evaporation technique.Using transmission electron microscopy and dynamic light scattering assays,it was determined the vaccines had a spherical structure with uniform particle size(643.5±35.3 nm).The nanomicrospheres possessed excellent encapsulation efficiency(81.6±2.6%)and loading rate(0.54±0.02%),and simultaneously exhibited negligible hemolytic activity and cell toxicity.The protection rate and tissue viral loads post-GCRV challenge in grass carp were assessed.The oral PP nano-microsphere with pVP4 t pIFN1(PP41)vaccine increased protection rate by 44%compared with the control group and was correlated with relatively low viral loads in the spleen,head kidney,and hindgut.Further,three crucial serum biochemical indexes,total superoxide dismutase(TSOD),complement C3(C3),and lysozyme(LZM),were also dramatically increased.Furthermore,mRNA expressions of representative immune-related genes(IgM,IFN1,IFNγ2,MHC-I,and CD8α)in the head kidney and spleen were significantly enhanced.In addition,mRNA expression of IgT was significantly boosted in the hindgut.The results indicate that DNA vaccine capsulated with PP is effective against GCRV infection.The present study provides insights into a prospective strategy for oral vaccine development in aquaculture.展开更多
The transcription factor Sex-determining region Y-box protein 3(SOX3)is well known for its critical roles in sex determination and cell differentiation;however,its function in antiviral innate immunity remains unexplo...The transcription factor Sex-determining region Y-box protein 3(SOX3)is well known for its critical roles in sex determination and cell differentiation;however,its function in antiviral innate immunity remains unexplored.This study uncovered how SOX3,induced by viral infections,modulates type Ⅰ interferon(IFN-Ⅰ)responses.RNA sequencing,quantitative PCR,and immunoblot analysis collectively revealed that SOX3 overexpression suppresses virus-induced interferon beta 1(IFN-β)promoter activation and significantly inhibits the expression of key antiviral interferon-stimulated genes(ISGs),including ISG15 and interferon induced protein with tetratricopeptide repeats 1(IFIT1).Conversely,the knockdown of SOX3 enhanced IFN-β production and ISGs expression,confirming its role as a negative regulator of antiviral immunity.Mechanistically,chromatin immunoprecipitation sequencing(ChIP-seq)identified SOX3 binding specifically at the AKT serine/threonine kinase 1(AKT1)locus.Further analysis demonstrated that SOX3 directly upregulates AKT1 expression,subsequently increasing phosphorylation and inactivation of the tumor suppressor phosphatase and tensin homolog(PTEN).Inactivation of PTEN inhibited interferon regulatory factor 3(IRF3)nuclear translocation,leading to reduced IFN-β expression.Thus,our findings uncover a previously uncharacterized SOX3-AKT1-PTEN signaling axis in the regulation of antiviral innate immunity,providing new insights into immune evasion strategies and highlighting potential therapeutic targets to enhance antiviral responses.展开更多
基金Supported by a grant from the Bundesministerium für Bildung und Forschung,No.FKZ 01ZZ0108
文摘AIM： To analyze and to compare the effects of interferon （IFN）-α, IFN-β, and IFN-γ on pancreatic stellate cell （PSC） activation/n vitro and to elucidate the molecular basis of IFN action. METHODS： PSCs were isolated from rat＇s pancreatic tissue, cultured and stimulated with recombinant rat IFNs. Cell proliferation and collagen synthesis were assessed by measuring the incorporation of 5-bromo-2＇ -deoxyuridine （BrdU） into DNA and [^3H]-proline into acetic acid-soluble proteins, respectively. Apoptotic ceils were determined by FACS analysis （sub-G1 peak method）. Exhibition of the myofibroblastic PSC phenotype was monitored by immunoblot analysis of （α-smooth muscle actin （α-SMA） expression. To assess the activation of signal transducer and activator of transcription （STAT）, Western blots using phospho- STAT-specific antibodies were performed. In studies on STAT1 function, expression of the protein was inhibited by siRNA. RESULTS： IFN-β and IFN-γ, but not IFN-α significantly diminished PSC proliferation and collagen synthesis. IFN-γ, was the only IFN that clearly inhibited α-SMA expression. Under the experimental conditions used, no enhanced rate of apoptotic cell death was observed in response to any IFN treatment. IFN-β and IFN-γ, induced a strong increase of STAT1 and STAT3 tyrosine phosphorylation, while the effect of IFN-α was much weaker. Inhibition of STAT1 expression with siRNA was associated with a significantly reduced growth-inhibitory effect of IFN-γ. CONCLUSION： IFN-β and particularly IFN-γ, display inhibitory effects on PSC activation in vitro and should be tested regarding their in vitro efficiency. Growth inhibition by IFN-γ action requires STAT1.
基金Supported by National Natural Science Foundation of China,No.81800855 and No.82070967Natural Science Foundation of Hunan Province,No.2018JJ3765.
文摘Diabetic retinopathy(DR)is one of the major causes of visual impairment and irreversible blindness in developed regions.Aside from abnormal angiogenesis,inflammation is the most specific and might be the initiating factor of DR.As a key participant in inflammation,interferon-gamma(IFN-γ)can be detected in different parts of the eye and is responsible for the breakdown of the blood-retina barrier and activation of inflammatory cells and other cytokines,which accelerate neovascularization and neuroglial degeneration.In addition,IFN-γis involved in other vascular complications of diabetes mellitus and angiogenesis-dependent diseases,such as diabetic nephropathy,cerebral microbleeds,and age-related macular degeneration.Traditional treatments,such as anti-vascular endothelial growth factor agents,vitrectomy,and laser photocoagulation therapy,are more effective for angiogenesis and not tolerable for every patient.Many ongoing clinical trials are exploring effective drugs that target inflammation.For instance,IFN-αacts against viruses and angiogenesis and is commonly used to treat malignant tumors.Moreover,IFN-αhas been shown to contribute to alleviating the progression of DR and other ocular diseases.In this review,we emphasize the roles that IFNs play in the pathogenesis of DR and discuss potential clinical applications of IFNs in DR,such as diagnosis,prognosis,and therapeutic treatment.
基金Supported by National Natural Science Foundation of China to Pei RJ and Chen XC,Nos.31200135 and 31200699German Research Foundation to Lu MG,Nos.TRR60,GK1045/2 and GK1949
文摘Hepatitis B virus (HBV) infection is one of the major causes of liver diseases, affecting more than 350 million people worldwide. The interferon (IFN)-mediated innate immune responses could restrict HBV replication at the different steps of viral life cycle. Indeed, IFN-α has been successfully used for treatment of patients with chronic hepatitis B. However, the role of the innate immune response in HBV replication and the mechanism of the anti-HBV effect of IFN-α are not completely explored. In this review, we summarized the currently available knowledge about the IFN-mediated anti-HBV effect in the HBV life cycle and the possible effectors downstream the IFN signaling pathway. The antiviral effect of Toll-like receptors (TLRs) in HBV replication is briefly discussed. The strategies exploited by HBV to evade the IFN- and TLR-mediated antiviral actions are summarized.
文摘Viruses are obligatory intracellular parasites. Most of the cells in animaland human body possess the innate ability to fight viruses. Innate immune function restrictsinfection at the early stage and delay spread of virus. The early stage of infection is the stage ofinteraction between the virus and the host's defence system. Once the latter is breached, the earlynon-specific or innate immune components such as interferon (IFN), natural killer (NK) cells andmacrophages become active. As the infection proceeds, the adaptive (specific) immune responsedevelops, with the appearance of cytotoxic T cells, helper T cells and antiviral antibodies.Antibodies provide a major barrier to virus spread between cells and cells and are particularlyimportant in restriction of virus spread in the blood stream. Virus infection directly activates thetranscription of type Ⅰ IFN (IFN-alfa/beta) genes in infected cells, while the type Ⅱ IFN(IFN-gamma) plays an essential role in the regulation of an adaptive immune response rather thaninnate immune response. Therefore, Type Ⅰ IFN is the first defence for host and neighbouring cellsto resist virus infection.
文摘Objective：To investigate the effects and mechanisms of interferon in combination with alltrans retinoic acid （ATRA） on proliferation and differentiation of ATRA-resistent APL cell. Methods ：After MR2 cells （ATRA-resistance cell line） were treated with IFN-α, IFN-γ and ATRA alone or IFN-α and IFN-γ in combination with ATRA respectively. The cell proliferation was tested by MTT test and the cell differentiation was tested through light microscope by NBT test and flow cytometry （FCM）. The expres sion of promyelocytic leukemia （PML） protein was observed by indirect immune fluorescent method. Results： Both IFN-α and IFN-γ could inhibit the proliferation and induce the differentiation of MR2 cells to some extent. The effects were more obvious after both interferons in combination with ATRA respectively （P〈0.05）. Moreover, the maturation of MR2 cells induced by IFN-γ＋ATRA group was more higher than that by IFN-α＋ATRA group （P〈0. 05）. Both interferons could induce the expressions of PML protein. Conclusion：Both interferons can inhibit MR2 cells proliferation, which may be related to the expression of PML protein induced by both interferons. The inducing differentiation effects of IFN-γ＋ATRA group on MR2 cells are more powerful than those of IFN-aq-ATRA group, which may be related to the different signal transduction pathway of both interferons.
基金supported by grants from the U.S.National Institutes of Health(Al163045 to KC)the Spanish Ministry of Science,Innovation and Universities(RTI2018-093894-B-100 to AC).
文摘Sjögren’s disease(SjD)is an autoimmune and inflammatory disease characterized by immune-mediated impairment of salivary and lacrimal gland functions,causing dryness in the mouth and eyes.SjD also involves other exocrine glands in the respiratory and gastrointestinal tracts and the skin and has a wide and variable range of extraglandular and systemic manifestations[1].
文摘Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/s41423-025-01353-z,published online 27 October 2025.The wrong article file was originally published;it has now been replaced with the correct file.The original article has been corrected.
基金This work was supported by the National Basic Research Program of China(No.2014CB541904)the National Natural Science Foundation of China(Nos.31470879 81571575 8171101311 and 31770960)+2 种基金the Interdisciplinary Innovation Team,External Cooperation Program(No.GJHZ201312)Key Project QYZDB-SSW-SMC036the Strategic Priority Research Program(No.XDPB0303),Chinese Academy of Sciences.
文摘A hallmark of systemic lupus erythematosus(SLE)is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies;however,the antibody-independent features of the B-cell compartment in SLE are less understood.In this study,we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients.We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients.Plasma from SLE patients potently promoted the survival of transitional B cells in a type I IFN-dependent manner,which can be recapitulated by direct IFN-αtreatment.Furthermore,the effect of IFN-αon enhanced survival of transitional B cells was associated with NF-κB pathway activation and reduced expression of the pro-apoptotic molecule Bax.Transitional B cells from SLE patients harbored a higher capacity to produce proinflammatory cytokine IL-6,which was also linked to the overactivated type I IFN pathway.In addition,the frequency of IL-6-producing transitional B cells was positively correlated with disease activity in SLE patients,and these cells were significantly reduced after short-term standard therapies.Thus,the current study provides a direct link between type I IFN pathway overactivation and the abnormally high frequency and proinflammatory properties of transitional B cells in active SLE patients,which contributes to the understanding of the roles of type I IFNs and B cells in the pathogenesis of SLE.
文摘Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cutaneous vasculopathy,and pulmonary inflammation.We sequenced a candidate gene,TMEM173,encoding the stimulator of interferon genes(STING),in this patient and in five unrelated children with similar clinical phenotypes.Four children were evaluated clinically and immunologically.With the STING ligand cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls,as well as commercially obtained endothelial cells,and then assayed transcription of IFNB1,the gene encoding interferon-β,in the stimulated cells.We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs.Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1(STAT1),so we tested the effect of Janus kinase(JAK)inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls.
基金supported by the National Natural Science Foundation of China(NSFC,Nos.32222090,32101069 and 32171318)Faculty of Health Sciences,University of Macao,the Multi-Year Research Grant(MYRG)of University of Macao+3 种基金the University of Macao Development Foundation(UMDF)(Nos.MYRG2022-00011-FHS and MYRG-GRG2023-00013-FHS-UMDF)the Science and Technology Development Fund,Macao SAR(Nos.0002/2021/AKP,0133/2022/A3,0009/2022/AKP,and 0006/2023/ITP1)Ministry of Education Frontiers Science Centre for Precision Oncology,University of Macao(No.SP2023-00001-FSCPO)Guangdong Provincial Applied Science and Technology Research and Development Program(No.2024A1515011140).
文摘The stimulator of interferon genes(STING),as a critical innate immune sensor,has been widely and continually explored in immune-related disease treatment.As lipid bilayer-closed particles derived from cells,extracellular vesicles(EVs)inherently function in target-guided intercellular communication.To incorporate the native merits of EVs into STING pathways,i.e.,engineered EV@STING,poor bioavailability and off-target issues that STING activators possess could be significantly overcome.In this review,emerged STING activators such as nitrogen-containing heterocyclic structures and the universal STING activation strategy(uniSTING)are firstly summarized.Diverse EVs sources from mesenchymal stem cells(MSCs)and innate and adaptive immune cells may evoke distinct regulatory results.Concurrently,how the EVs contents including double-stranded DNA(dsDNA),microRNA(miRNA),cyclic GMP-AMP synthase(cGAS)and 2′3′-cyclic GMP-AMP(2′3′-cGAMP)proteins participate in the regulation of STING activation are widely studied.After mastering the two pivotal aspects of EV@STING,their immunomodulatory roles including in pathogen infection,inflammatory diseases,and cancer therapy are comprehensively summed up and discussed.Finally,in cancer study field,therapeutic challenges and clinical translational opportunities of EV@STING are thoroughly evaluated.
基金supported by the National Natural Science Foundation of China(Grant No.82220108002 to F.C.and Grant No.82273737 to R.Z.)the U.S.National Institutes of Health(Grant Nos.CA209414,HL060710,and ES000002 to D.C.C.,Grant Nos.CA209414 and CA249096 to Y.L.)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.
文摘Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.
文摘Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cutaneous vasculopathy,and pulmonary inflammation.We sequenced a candidate gene,TMEM173,encoding the stimulator of interferon genes(STING),in this patient and in five unrelated children with similar clinical phenotypes.
基金Guangdong Province Medical Research Fund Project,Grant/Award Number:B2024112The Scientific Research Special Project of the Joint Construction Project of High-level Hospitals between Guangzhou University of Chinese Medicine and the Scientific Research Fund Project,Grant/Award Number:GZYZS2024G09+2 种基金Special Project of the Research Platform of Guangdong Provincial Department of Traditional Chinese Medicine,Grant/Award Number:20254040the Project of the Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory/Hengqin Laboratory,Grant/Award Number:HQL2024PZ043Guangdong Province Natural Science Foundation-Guangzhou-South China Joint Youth Fund Project,Grant/Award Number:2023A1515110849。
文摘Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever using interferon type I(IFN-I)or combined IFN-I/II receptor knockout mice infected with dengue virus(DENV).However,this model requires further optimization to better support related studies.Methods:This study aimed to establish a stable dengue infection model by evaluating the effects of different genetic backgrounds and injection routes on DENV infection in interferon receptor knockout mice.We first infected various strains of interferon receptor-deficient mice with DENV and compared their susceptibility based on clini-cal symptoms,viremia levels,organ indices,histopathological findings,and vascular leakage markers.Subsequently,we selected the most susceptible strain to further investigate the impact of different injection methods on infection outcomes.Results:We found that BALB/c background mice with type 1 interferon recep-tor knockout(IFNAR)had the most obvious symptoms.Subsequently,we selected IFNAR−/−BALB/c mice to further explore the effects of different injection methods on dengue virus infection.The results showed that the intraperitoneal injection group had the most severe clinical symptoms,the longest duration of viremia,and the most obvious degree of organ damage.Conclusion:Through systematic screening and optimization,we established a robust animal model of dengue virus infection via intraperitoneal injection in IFNAR−/−BALB/c mice.This model offers a valuable tool for future dengue research.
文摘Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of all the autoimmune rheumatic diseases,SSc has the highest all-cause mortality rate,and the underlying pathogenic processes that mediate disease are still obscure,with wide diff erences in presentation and progression[2,3].
文摘Purpose To review the efficacy and safety of pegylated interferons (peginterferons) in the treatment of chronic hepatitis C Data sources An English language literature search (MEDLINE 1988-2001) was performed and a total of 19 original articles related to the issue were selected Data extraction After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria The papers reviewed pertained mainly to the efficacy and safety profiles of peginterferons in the treatment of chronic hepatitis C Results Peginterferon can effectively prolong the half-life of interferon and can be effectively administered conveniently as a once-a-week dose The antiviral effect using peginterferon was enhanced compared with that of standard interferon, but the frequency and severity of adverse events were typical of those associated with interferon-α Conclusions Based on its efficacy, safety and convenient dosing, peginterferon is more favorable than standard interferon in the treatment of chronic hepatitis C
文摘The mammalian innate immune system provides the first line of defensive mechanisms to protect the host against invading pathogens.These defensive responses are initiated by recognition of microbial pathogen-associated molecular patterns(PAMPs).
基金a grant from the Korea Healthcare Technology R&D Project(A080489)Ministry of Health&Welfare,Korea,and by Grant No.RTI05-01-01 from the Regional Technology Innovation Program of the Ministry of Commerce,Industry and Energy,Korea.
文摘The major limitation for the maturation of dendritic cells(DCs)using Toll-like receptor(TLR)agonists is their decreased ability to migrate into lymph nodes compared with conventional DCs.CD38 can be used as a multifunctional marker to modulate migration,survival and Th1 responses of DCs.CD74 has been shown to negatively regulate DC migration.The goal of this study was to investigate the combinations of TLR agonists and interferons(IFNs)that most effectively regulate CD38 and CD74 expression on DCs.Synergistic TLR agonist stimulation in combination with IFN-a and IFN-c was the best method for regulating CD38 and CD74 expression and inducing the highest secretion of IL-12p70.An in vitro migration assay showed that DCs treated with this combination had significantly enhanced migratory ability,similar to that observed in cells expressing CD38,CD74 and CCR7.The results of this study suggest that an alternative maturation protocol in which two TLR ligands are combined with type I and II IFNs generates potent DCs that have both a high migratory capacity and high IL-12p70 production.
文摘It is well known that interferons are potential antivirus proteins and possess anticancer capability. In the Thirty-fifth Symposium of the Society for General Microbiology on Interferons held in 1983, Hans Strander reported that interferons had been successfully applied in the treatment of juvenile laryngeal papilloma, papilloma accuminatum, malignant mydomatosis, osteosarcoma, breast cancer, cancer of the colon, non-Hodgkin lymphoma,
基金supported by the National Key R&D Program of China(2022YFF1000302)Major Project of Hubei Hongshan Laboratory(2022hszd011).
文摘Grass carp hemorrhagic disease caused by grass carp reovirus(GCRV)results in significant economic losses to the global grass carp aquaculture industry.Oral vaccination is an ideal choice for disease precaution in aquaculture.However,oral vaccine can be degraded in the gut.Therefore,the selection of loading materials is essential.In this study,the S6 and S7 fragments(encoding the outer capsid protein VP4 and fibronectin VP56 of GCRV)and grass carp interferons(IFNs),including IFN1,IFN3,and IFNγ2 were used to create DNA vaccines and adjuvants based on pcDNA3.1,respectively.The oral DNA vaccine was encapsulated in poly(lactic-co-glycolic acid)(PLGA)and polyvinyl alcohol(PVA)with IFNs.The PLGA-PVA(PP)nano-microspheres were prepared by double emulsionsolvent evaporation technique.Using transmission electron microscopy and dynamic light scattering assays,it was determined the vaccines had a spherical structure with uniform particle size(643.5±35.3 nm).The nanomicrospheres possessed excellent encapsulation efficiency(81.6±2.6%)and loading rate(0.54±0.02%),and simultaneously exhibited negligible hemolytic activity and cell toxicity.The protection rate and tissue viral loads post-GCRV challenge in grass carp were assessed.The oral PP nano-microsphere with pVP4 t pIFN1(PP41)vaccine increased protection rate by 44%compared with the control group and was correlated with relatively low viral loads in the spleen,head kidney,and hindgut.Further,three crucial serum biochemical indexes,total superoxide dismutase(TSOD),complement C3(C3),and lysozyme(LZM),were also dramatically increased.Furthermore,mRNA expressions of representative immune-related genes(IgM,IFN1,IFNγ2,MHC-I,and CD8α)in the head kidney and spleen were significantly enhanced.In addition,mRNA expression of IgT was significantly boosted in the hindgut.The results indicate that DNA vaccine capsulated with PP is effective against GCRV infection.The present study provides insights into a prospective strategy for oral vaccine development in aquaculture.
基金supported by the Central Guidance on Local Science and Technology Development Fund of Tibet(Grant No.XZ202301YD0040C)the National Natural Science Foundation of China(Grant No.32260173)the Youth Program of Natural Science Foundation of Henan Province(Grant No.252300420594).
文摘The transcription factor Sex-determining region Y-box protein 3(SOX3)is well known for its critical roles in sex determination and cell differentiation;however,its function in antiviral innate immunity remains unexplored.This study uncovered how SOX3,induced by viral infections,modulates type Ⅰ interferon(IFN-Ⅰ)responses.RNA sequencing,quantitative PCR,and immunoblot analysis collectively revealed that SOX3 overexpression suppresses virus-induced interferon beta 1(IFN-β)promoter activation and significantly inhibits the expression of key antiviral interferon-stimulated genes(ISGs),including ISG15 and interferon induced protein with tetratricopeptide repeats 1(IFIT1).Conversely,the knockdown of SOX3 enhanced IFN-β production and ISGs expression,confirming its role as a negative regulator of antiviral immunity.Mechanistically,chromatin immunoprecipitation sequencing(ChIP-seq)identified SOX3 binding specifically at the AKT serine/threonine kinase 1(AKT1)locus.Further analysis demonstrated that SOX3 directly upregulates AKT1 expression,subsequently increasing phosphorylation and inactivation of the tumor suppressor phosphatase and tensin homolog(PTEN).Inactivation of PTEN inhibited interferon regulatory factor 3(IRF3)nuclear translocation,leading to reduced IFN-β expression.Thus,our findings uncover a previously uncharacterized SOX3-AKT1-PTEN signaling axis in the regulation of antiviral innate immunity,providing new insights into immune evasion strategies and highlighting potential therapeutic targets to enhance antiviral responses.
