BACKGROUND T helper 17(Th17)cell infiltration and interleukin(IL)-17 secretion in intrahepatic small bile ducts is a critical driver of immune-mediated injury in primary biliary cholangitis(PBC).IL-6 is an essential u...BACKGROUND T helper 17(Th17)cell infiltration and interleukin(IL)-17 secretion in intrahepatic small bile ducts is a critical driver of immune-mediated injury in primary biliary cholangitis(PBC).IL-6 is an essential upstream activator of Th17 cells.Basophilderived IL-6 promotes the differentiation of CD4+T cells and Th1 cells into Th17 cells,thereby regulating their immunological functions.AIM To investigate the activation status and cytokine expression of basophils in PBC,elucidating potential mechanisms through which basophils contribute to its pathogenesis.METHODS This single-center retrospective case-control study conducted at Guangdong Medical University Affiliated Hospital(China)between September 2019 and August 2024 enrolled 65 consecutive treatment-naïve patients with PBC(PBC group),65 age-and sex-matched patients with chronic hepatitis B(CHB group),and 65 healthy controls(Normal group).Fourteen participants per group(subgroup)were randomly selected for flow cytometry analysis of basophil proportion,activation markers(CD203c and CD62 L mean fluorescence intensity),IL-6-positive basophils(IL-6+basophils as a percentage of total basophils),and IL-17-positive T lymphocytes(CD3+CD4+IL-17+cells)proportion among T cells.Data were analyzed using Kruskal-Wallis and χ^(2) tests as appropriate.RESULTS Routine blood tests revealed significantly higher basophil counts and proportions in the PBC group compared to the CHB and Normal groups(P<0.001 for both comparisons),with no significant differences between the CHB and Normal groups(P=0.201).Flow cytometry revealed a higher basophil proportion in the PBC subgroup compared to the CHB(P=0.011)and Normal subgroups(P<0.001).The mean fluorescence intensity of CD203c on basophil surfaces was elevated in the PBC subgroup compared to the CHB(P=0.032)and Normal subgroups(P=0.039).The proportion of IL-6+basophils was significantly higher in the PBC subgroup than in the CHB(P<0.01)and Normal subgroups(P<0.001).Similarly,the Th17 cell proportion was markedly elevated in the PBC compared to the CHB(P<0.001)and Normal subgroups(P<0.001).CONCLUSION Patients with PBC have increased peripheral basophil counts with enhanced activation.Activated basophils have increased IL-6 expression,which may indirectly induce Th17 cell proliferation and contribute to PBC pathogenesis.展开更多
Using two-colour flow cytometry>200 antibodies submitted to the 8^(th) International Workshop of Human Leukocyte Differentiation Antigens(HLDA8)have been analyzed for their reactivity with resting and activated CD2...Using two-colour flow cytometry>200 antibodies submitted to the 8^(th) International Workshop of Human Leukocyte Differentiation Antigens(HLDA8)have been analyzed for their reactivity with resting and activated CD203c^(+)basophils.Four antibodies either non-reactive or weakly reactive with resting basophils exhibited an increased reactivity with basophils activated by anti-IgE-mediated cross-linking of the high affinity IgE receptor(FcεRI).These include antibod-ies against CD164(WS-80160,clone N6B6 and WS-80162,clone 67D2),as well as two reagents with previously unknown specificities that were identified as CD13(WS-80274,clone A8)and CD107a(WS-80280,clone E63-880).The activation patterns followed either the“CD203c-like”or“CD63-like”activation profile.The CD203c profile is characterized by a rapid and significant upregulation(of CD13,CD164,and CD203c),reaching maximum levels after 5-15 min of stimulation.The phosphoinositide-3-kinase(PI3K)-specific inhibitor wortmannin inhibited the upregulation of these markers whereas 12-O-tetradecanoyl-phorbol-13-acetate(TPA)induced a rapid and FcεRI-independent upregulation within 1-2 min.In the CD63 profile,maximum upregulation(of CD63 and CD107a)was detected only after 20-40 min,and upregulation by TPA reached maximum levels after 60 min.In summary,our data identify CD13,CD107a,and CD164 as novel basophil-activation antigens.Based on time kinetics of upregulation,we hypothesize that molecules of the“CD203c group”and the“CD63 group”are linked to two different mechanisms of basophil activation.展开更多
Basophils,which are considered as redundant relatives of mast cells and the rarest granulocytes in peripheral circulation,have been neglected by researchers in the past decades.Previous studies have revealed their vit...Basophils,which are considered as redundant relatives of mast cells and the rarest granulocytes in peripheral circulation,have been neglected by researchers in the past decades.Previous studies have revealed their vital roles in allergic diseases and parasitic infections.Intriguingly,recent studies even reported that basophils might be associated with cancer development,as activated basophils synthesize and release a variety of cytokines and chemokines in response to cancers.However,it is still subject to debate whether basophils function as tumor-protecting or tumor-promoting components;the answer may depend on the tumor biology and the microenvironment.Herein,we reviewed the role of basophils in cancers,and highlighted some potential and promising therapeutic strategies.展开更多
AIM:To evaluate the mechanism of which brimonidine tartrate 0.15%causes clinical hypersensitivity.METHODS:A prospective case-control study comparing 8 glaucoma patients with clinical hypersensitivity to brimonidine to...AIM:To evaluate the mechanism of which brimonidine tartrate 0.15%causes clinical hypersensitivity.METHODS:A prospective case-control study comparing 8 glaucoma patients with clinical hypersensitivity to brimonidine to a control group consisting 13 healthy volunteers.Blood samples were stimulated with brimonidine 0.15%,timolol 0.5%or brimonidine tartrate/timolol maleate 0.2%/0.5%.Premixed antibodies(CD63/FITC and aIgE/PE)were added for direct staining and whole-blood samples were lysed,fixed and analyzed by a flow cytometer.The basophil population was defined by high IgE cell expression.Degranulation was identified by the expression of the activation molecule CD63.RESULTS:Basophil activation was not significant when comparing percent of activated basophils of patients and healthy controls after exposure to brimonidine(2.58%,2.45%,respectively,P=0.72).There was a significant suppression of basophil activation when a combination of brimonidine-timolol(0.87%)was compared to timolol(2.27%;P=0.012)and to brimonidine alone(2.58%;P=0.017).CONCLUSION:The results of our study do not support the hypothesis that brimonidine induces an immediate allergic reaction.Basophil activation was suppressed by the presence ofβ-blockers in patients hypersensitive to brimonidine and in healthy individuals.This finding indicates that timolol suppress brimonidine drug reaction by a different mechanism.展开更多
Biomaterials for restoration or replacement of diseased tissues may have any origin.The major characteristic for biomaterials is biocompatibility.All biomaterials,used in medicine (dentistry,in particular),interreact ...Biomaterials for restoration or replacement of diseased tissues may have any origin.The major characteristic for biomaterials is biocompatibility.All biomaterials,used in medicine (dentistry,in particular),interreact with the organism tissues.And the changes occur both in the materials and the organism tissues.It is considered that there are no "inert biomaterials." The number of allergic diseases and complications is constantly growing all over the world,taking an important place in the structure of infectious and noninfectious pathology[1].Pollen,household,epidermal,and food-borne allergens,and haptens are the most frequent sources of sensibilization.展开更多
Background Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-ind...Background Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles of β1 and β2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase （PI3K）, src-kinases and extracellular signal regulated kinase （ERK）1/2 in basophil adhesion and histamine release （HR）. Methods Basophils （purity of 10%-50%） were preincubated with anti-CD29 or anti-CD 18 blocking antibodies before used for adhesion study. Basophils were preincubated with the pharmacological inhibitors wortmannin, PP1, PD98059 before used for adhesion and HR study. Cell adherence to bovine serum albumin （BSA） or fibronectin （Fn） was monitored using cell associated histamine as a basophil marker and the histamine was measured by the glass fiber assay. Results Basophil spontaneous adhesion to Fn was inhibited by anti-CD29. Interleukin （IL）-3, granulocyte/macrophage colony stimulating factor （GM-CSF） induced adhesion to BSA was inhibited by anti-CD18. Wortmannin at 1 μmol/L and PP1 at 20 μmol/L strongly interfered with, whereas PD98059 at 50μmol/L weakly inhibited basophil spontaneous adhesion to Fn. One μmol/L wortmannin strongly inhibited IL-3, IL-5, GM-CSF and anti-IgE induced adhesion to BSA. PP1 at 20 μmol/L partly inhibited anti-IgE induced adhesion. Fifty μmol/L PD98059 marginally inhibited IL-5, weakly inhibited anti-IgE, partly inhibited GM-CSF induced adhesion. Wortmannin, PP1 and PD98059 inhibited anti-IgE （1：100 or 1：1000） induced basophil HR in a dose dependent manner. They inhibited calcium ionophore A23187 （10 μmol/L, 5 μmol/L） induced basophil HR in a dose dependent manner, but to different extend with PP1 being the most efficient. Conclusions Basophil spontaneous adhesion to Fn is mediated by β 1-integrins whereas cytokine induced adhesion to BSA is mediated by β 2-integrins. PI3K, src-kinases and ERK1/2 play distinct signaling roles in basophil adhesion and HR. PI3K is the key player while ERK1/2 is the weakest participant.展开更多
The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mech...The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 （NOD2） and toll-like receptor 2 （TLR2） ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions, Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil-fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway bv which S. aureus contributes to the DathoDhvsiology of AD.展开更多
Acute basophilic leukemia （ABL） is a rare subtype of .acute myeloid leukemia （AML）, accounting for 4%-5% of AML and less than 2% of all hematopoietic malignancies. It is usually characterized by a very rapid clini...Acute basophilic leukemia （ABL） is a rare subtype of .acute myeloid leukemia （AML）, accounting for 4%-5% of AML and less than 2% of all hematopoietic malignancies. It is usually characterized by a very rapid clinical course, symptoms of hyperhistaminemia, peptic ulceration, gastrointestinal cerebrovascular bleeding and resistance to therapy.^1 However, the clinical outcome of ABL remains disapp2ointing. Most patients died within 1 year after diagnosis.展开更多
Allergic diseases,mainly mediated by T helper type 2(Th2)immunity,have become a worldwide public health problem.Traditional Chinese medicine(TCM)has long been used in treating and preventing allergic symptoms.As the n...Allergic diseases,mainly mediated by T helper type 2(Th2)immunity,have become a worldwide public health problem.Traditional Chinese medicine(TCM)has long been used in treating and preventing allergic symptoms.As the new target of anti-allergy TCM,basophils,after approximately 140 years since their discovery,are just now gaining respect as important contributors in the pathogenesis underlying allergic inflammation and disease.In addition to their role as effector cells,basophils can release early IL-4,migrate from circulatory system into draining lymph nodes,present antigen to naive CD4^+T cells,and promote the differentiation of Th2 cells.Herein,we briefly summarized the recent research advances of the essential contributions of basophils in the initiation of Th2 immune responses.展开更多
Recombinant interleukin-33(IL-33)inhibits tumor growth,but the detailed immunological mechanism is still unknown.IL-33-mediated tumor suppression did not occur in Batf3^(−/−)mice,indicating that conventional type 1 de...Recombinant interleukin-33(IL-33)inhibits tumor growth,but the detailed immunological mechanism is still unknown.IL-33-mediated tumor suppression did not occur in Batf3^(−/−)mice,indicating that conventional type 1 dendritic cells(cDC1s)play a key role in IL-33-mediated antitumor immunity.A population of CD103^(+)cDC1s,which were barely detectable in the spleens of normal mice,increased significantly in the spleens of IL-33-treated mice.The newly emerged splenic CD103^(+)cDC1s were distinct from conventional splenic cDC1s based on their spleen residency,robust effector T-cell priming ability,and surface expression of FCGR3.DCs and DC precursors did not express Suppressor of Tumorigenicity 2(ST2).However,recombinant IL-33 induced spleen-resident FCGR3^(+)CD103^(+)cDC1s,which were found to be differentiated from DC precursors by bystander ST2+immune cells.Through immune cell fractionation and depletion assays,we found that IL-33-primed ST2^(+)basophils play a crucial role in the development of FCGR3^(+)CD103^(+)cDC1s by secreting IL-33-driven extrinsic factors.Recombinant GM-CSF also induced the population of CD103^(+)cDC1s,but the population neither expressed FCGR3 nor induced any discernable antitumor immunity.The population of FCGR3^(+)CD103^(+)cDC1s was also generated in vitro culture of Flt3L-mediated bone marrow-derived DCs(FL-BMDCs)when IL-33 was added in a pre-DC stage of culture.FL-BMDCs generated in the presence of IL-33(FL-33-DCs)offered more potent tumor immunotherapy than control Flt3L-BMDCs(FL-DCs).Human monocyte-derived DCs were also more immunogenic when exposed to IL-33-induced factors.Our findings suggest that recombinant IL-33 or an IL-33-mediated DC vaccine could be an attractive protocol for better tumor immunotherapy.展开更多
基金Supported by Guangdong Provincial Basic and Applied Basic Research Fund,No.2021A1515011589Guangdong Medical University Clinical+Basic Science and Technology Innovation Special Program,No.GDMULCJC2024004.
文摘BACKGROUND T helper 17(Th17)cell infiltration and interleukin(IL)-17 secretion in intrahepatic small bile ducts is a critical driver of immune-mediated injury in primary biliary cholangitis(PBC).IL-6 is an essential upstream activator of Th17 cells.Basophilderived IL-6 promotes the differentiation of CD4+T cells and Th1 cells into Th17 cells,thereby regulating their immunological functions.AIM To investigate the activation status and cytokine expression of basophils in PBC,elucidating potential mechanisms through which basophils contribute to its pathogenesis.METHODS This single-center retrospective case-control study conducted at Guangdong Medical University Affiliated Hospital(China)between September 2019 and August 2024 enrolled 65 consecutive treatment-naïve patients with PBC(PBC group),65 age-and sex-matched patients with chronic hepatitis B(CHB group),and 65 healthy controls(Normal group).Fourteen participants per group(subgroup)were randomly selected for flow cytometry analysis of basophil proportion,activation markers(CD203c and CD62 L mean fluorescence intensity),IL-6-positive basophils(IL-6+basophils as a percentage of total basophils),and IL-17-positive T lymphocytes(CD3+CD4+IL-17+cells)proportion among T cells.Data were analyzed using Kruskal-Wallis and χ^(2) tests as appropriate.RESULTS Routine blood tests revealed significantly higher basophil counts and proportions in the PBC group compared to the CHB and Normal groups(P<0.001 for both comparisons),with no significant differences between the CHB and Normal groups(P=0.201).Flow cytometry revealed a higher basophil proportion in the PBC subgroup compared to the CHB(P=0.011)and Normal subgroups(P<0.001).The mean fluorescence intensity of CD203c on basophil surfaces was elevated in the PBC subgroup compared to the CHB(P=0.032)and Normal subgroups(P=0.039).The proportion of IL-6+basophils was significantly higher in the PBC subgroup than in the CHB(P<0.01)and Normal subgroups(P<0.001).Similarly,the Th17 cell proportion was markedly elevated in the PBC compared to the CHB(P<0.001)and Normal subgroups(P<0.001).CONCLUSION Patients with PBC have increased peripheral basophil counts with enhanced activation.Activated basophils have increased IL-6 expression,which may indirectly induce Th17 cell proliferation and contribute to PBC pathogenesis.
基金This work was supported by a grant from the Deutsche Forschungsgemeinschaft,SFB 510-A1(F.H.and H.-J.B.),by the fortueneproject F1282700 of the univer-sity of Tuebingen(H.-J.B)by the Fonds zur Forderung der wissnschaflichen Forschung in Osterreich,SFB grant-project 018/09(P.V.).
文摘Using two-colour flow cytometry>200 antibodies submitted to the 8^(th) International Workshop of Human Leukocyte Differentiation Antigens(HLDA8)have been analyzed for their reactivity with resting and activated CD203c^(+)basophils.Four antibodies either non-reactive or weakly reactive with resting basophils exhibited an increased reactivity with basophils activated by anti-IgE-mediated cross-linking of the high affinity IgE receptor(FcεRI).These include antibod-ies against CD164(WS-80160,clone N6B6 and WS-80162,clone 67D2),as well as two reagents with previously unknown specificities that were identified as CD13(WS-80274,clone A8)and CD107a(WS-80280,clone E63-880).The activation patterns followed either the“CD203c-like”or“CD63-like”activation profile.The CD203c profile is characterized by a rapid and significant upregulation(of CD13,CD164,and CD203c),reaching maximum levels after 5-15 min of stimulation.The phosphoinositide-3-kinase(PI3K)-specific inhibitor wortmannin inhibited the upregulation of these markers whereas 12-O-tetradecanoyl-phorbol-13-acetate(TPA)induced a rapid and FcεRI-independent upregulation within 1-2 min.In the CD63 profile,maximum upregulation(of CD63 and CD107a)was detected only after 20-40 min,and upregulation by TPA reached maximum levels after 60 min.In summary,our data identify CD13,CD107a,and CD164 as novel basophil-activation antigens.Based on time kinetics of upregulation,we hypothesize that molecules of the“CD203c group”and the“CD63 group”are linked to two different mechanisms of basophil activation.
基金supported by the Shanghai Sailing Program(No.21YF1407100)the China Postdoctoral Science Foundation(No.2021M690037)+1 种基金the National Natural Science Foundation of China(Nos.82103409 and 81773068)the National Key R&D Program of China(No.2019YFC1315902)。
文摘Basophils,which are considered as redundant relatives of mast cells and the rarest granulocytes in peripheral circulation,have been neglected by researchers in the past decades.Previous studies have revealed their vital roles in allergic diseases and parasitic infections.Intriguingly,recent studies even reported that basophils might be associated with cancer development,as activated basophils synthesize and release a variety of cytokines and chemokines in response to cancers.However,it is still subject to debate whether basophils function as tumor-protecting or tumor-promoting components;the answer may depend on the tumor biology and the microenvironment.Herein,we reviewed the role of basophils in cancers,and highlighted some potential and promising therapeutic strategies.
文摘AIM:To evaluate the mechanism of which brimonidine tartrate 0.15%causes clinical hypersensitivity.METHODS:A prospective case-control study comparing 8 glaucoma patients with clinical hypersensitivity to brimonidine to a control group consisting 13 healthy volunteers.Blood samples were stimulated with brimonidine 0.15%,timolol 0.5%or brimonidine tartrate/timolol maleate 0.2%/0.5%.Premixed antibodies(CD63/FITC and aIgE/PE)were added for direct staining and whole-blood samples were lysed,fixed and analyzed by a flow cytometer.The basophil population was defined by high IgE cell expression.Degranulation was identified by the expression of the activation molecule CD63.RESULTS:Basophil activation was not significant when comparing percent of activated basophils of patients and healthy controls after exposure to brimonidine(2.58%,2.45%,respectively,P=0.72).There was a significant suppression of basophil activation when a combination of brimonidine-timolol(0.87%)was compared to timolol(2.27%;P=0.012)and to brimonidine alone(2.58%;P=0.017).CONCLUSION:The results of our study do not support the hypothesis that brimonidine induces an immediate allergic reaction.Basophil activation was suppressed by the presence ofβ-blockers in patients hypersensitive to brimonidine and in healthy individuals.This finding indicates that timolol suppress brimonidine drug reaction by a different mechanism.
文摘Biomaterials for restoration or replacement of diseased tissues may have any origin.The major characteristic for biomaterials is biocompatibility.All biomaterials,used in medicine (dentistry,in particular),interreact with the organism tissues.And the changes occur both in the materials and the organism tissues.It is considered that there are no "inert biomaterials." The number of allergic diseases and complications is constantly growing all over the world,taking an important place in the structure of infectious and noninfectious pathology[1].Pollen,household,epidermal,and food-borne allergens,and haptens are the most frequent sources of sensibilization.
基金this study was supported by grants from the Danish Allergy Research Center, the Foundation for the Excellent Young Scientist of Anhui Province (No. 04043053) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.
文摘Background Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles of β1 and β2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase （PI3K）, src-kinases and extracellular signal regulated kinase （ERK）1/2 in basophil adhesion and histamine release （HR）. Methods Basophils （purity of 10%-50%） were preincubated with anti-CD29 or anti-CD 18 blocking antibodies before used for adhesion study. Basophils were preincubated with the pharmacological inhibitors wortmannin, PP1, PD98059 before used for adhesion and HR study. Cell adherence to bovine serum albumin （BSA） or fibronectin （Fn） was monitored using cell associated histamine as a basophil marker and the histamine was measured by the glass fiber assay. Results Basophil spontaneous adhesion to Fn was inhibited by anti-CD29. Interleukin （IL）-3, granulocyte/macrophage colony stimulating factor （GM-CSF） induced adhesion to BSA was inhibited by anti-CD18. Wortmannin at 1 μmol/L and PP1 at 20 μmol/L strongly interfered with, whereas PD98059 at 50μmol/L weakly inhibited basophil spontaneous adhesion to Fn. One μmol/L wortmannin strongly inhibited IL-3, IL-5, GM-CSF and anti-IgE induced adhesion to BSA. PP1 at 20 μmol/L partly inhibited anti-IgE induced adhesion. Fifty μmol/L PD98059 marginally inhibited IL-5, weakly inhibited anti-IgE, partly inhibited GM-CSF induced adhesion. Wortmannin, PP1 and PD98059 inhibited anti-IgE （1：100 or 1：1000） induced basophil HR in a dose dependent manner. They inhibited calcium ionophore A23187 （10 μmol/L, 5 μmol/L） induced basophil HR in a dose dependent manner, but to different extend with PP1 being the most efficient. Conclusions Basophil spontaneous adhesion to Fn is mediated by β 1-integrins whereas cytokine induced adhesion to BSA is mediated by β 2-integrins. PI3K, src-kinases and ERK1/2 play distinct signaling roles in basophil adhesion and HR. PI3K is the key player while ERK1/2 is the weakest participant.
文摘The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 （NOD2） and toll-like receptor 2 （TLR2） ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions, Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil-fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway bv which S. aureus contributes to the DathoDhvsiology of AD.
文摘Acute basophilic leukemia （ABL） is a rare subtype of .acute myeloid leukemia （AML）, accounting for 4%-5% of AML and less than 2% of all hematopoietic malignancies. It is usually characterized by a very rapid clinical course, symptoms of hyperhistaminemia, peptic ulceration, gastrointestinal cerebrovascular bleeding and resistance to therapy.^1 However, the clinical outcome of ABL remains disapp2ointing. Most patients died within 1 year after diagnosis.
基金supported by the National Natural Science Foundation of China(NSFC)(No.81873066).
文摘Allergic diseases,mainly mediated by T helper type 2(Th2)immunity,have become a worldwide public health problem.Traditional Chinese medicine(TCM)has long been used in treating and preventing allergic symptoms.As the new target of anti-allergy TCM,basophils,after approximately 140 years since their discovery,are just now gaining respect as important contributors in the pathogenesis underlying allergic inflammation and disease.In addition to their role as effector cells,basophils can release early IL-4,migrate from circulatory system into draining lymph nodes,present antigen to naive CD4^+T cells,and promote the differentiation of Th2 cells.Herein,we briefly summarized the recent research advances of the essential contributions of basophils in the initiation of Th2 immune responses.
基金the National Research Foundation of Korea(SRC-2017R1A5A1014560). This work was supported by grants from the National Research Foundation of Korea(SRC-2017R1A5A1014560)。
文摘Recombinant interleukin-33(IL-33)inhibits tumor growth,but the detailed immunological mechanism is still unknown.IL-33-mediated tumor suppression did not occur in Batf3^(−/−)mice,indicating that conventional type 1 dendritic cells(cDC1s)play a key role in IL-33-mediated antitumor immunity.A population of CD103^(+)cDC1s,which were barely detectable in the spleens of normal mice,increased significantly in the spleens of IL-33-treated mice.The newly emerged splenic CD103^(+)cDC1s were distinct from conventional splenic cDC1s based on their spleen residency,robust effector T-cell priming ability,and surface expression of FCGR3.DCs and DC precursors did not express Suppressor of Tumorigenicity 2(ST2).However,recombinant IL-33 induced spleen-resident FCGR3^(+)CD103^(+)cDC1s,which were found to be differentiated from DC precursors by bystander ST2+immune cells.Through immune cell fractionation and depletion assays,we found that IL-33-primed ST2^(+)basophils play a crucial role in the development of FCGR3^(+)CD103^(+)cDC1s by secreting IL-33-driven extrinsic factors.Recombinant GM-CSF also induced the population of CD103^(+)cDC1s,but the population neither expressed FCGR3 nor induced any discernable antitumor immunity.The population of FCGR3^(+)CD103^(+)cDC1s was also generated in vitro culture of Flt3L-mediated bone marrow-derived DCs(FL-BMDCs)when IL-33 was added in a pre-DC stage of culture.FL-BMDCs generated in the presence of IL-33(FL-33-DCs)offered more potent tumor immunotherapy than control Flt3L-BMDCs(FL-DCs).Human monocyte-derived DCs were also more immunogenic when exposed to IL-33-induced factors.Our findings suggest that recombinant IL-33 or an IL-33-mediated DC vaccine could be an attractive protocol for better tumor immunotherapy.
