Idiopathic pulmonary fibrosis(IPF)is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function...Idiopathic pulmonary fibrosis(IPF)is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function.Chronic inflammation has been demonstrated to be the pathological basis of fibrosis.Emerging studies have revealed that most interleukin-17(IL-17)isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity.Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes,including the initiation and exacerbation of IPF.Here,we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.展开更多
Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approach...Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.展开更多
Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of ...Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear.In this study,we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A(IL-17)stimulation in SLE patients and lupus mice.Using a humanized lupus mouse model,we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs.Moreover,long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+subsets among IL-17 receptor-expressing plasma cells.Lupus mice deficient in IL-17 or IL-17 receptor C(IL-17RC)exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage,while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice.In reconstituted chimeric mice,IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells.Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization.Together,our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis,which may provide new therapeutic strategies for the treatment of SLE.展开更多
Objective: This study was carried out to test the effects of methotrexate (MTX) and black seed oil (BSO) on pristane-induced arthritis (PIA) in rats.Methods: Inbred dark agouti (DA) rats were induced by a single subcu...Objective: This study was carried out to test the effects of methotrexate (MTX) and black seed oil (BSO) on pristane-induced arthritis (PIA) in rats.Methods: Inbred dark agouti (DA) rats were induced by a single subcutaneous injection of pristane,and then treated with MTX or BSO.Arthritis severity was evaluated macroscopically and microscopically.Plasma nitric oxide (NO) concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-time reverse transcription-polymerase chain reaction (RT-PCR).Results: The clinical arthritis severity was decreased after MTX treatment,while the BSO groups did not show significant changes compared with the disease group.The plasma NO level of the MTX group was significantly decreased compared with the disease group,but the BSO groups showed no difference from the disease group in plasma NO levels.The interferon-γ (IFN-γ) and interleukin-17A (IL-17A) mRNA expressions in the spleens were significantly decreased in the MTX group,but only showed a declining trend in the BSO groups compared with the disease group.Neither MTX nor BSO had an effect on the mRNA expressions of IL-4,transforming growth factor β (TGF-β),and tumor necrosis factor-α (TNF-α) in the spleen.Conclusions: MTX,but not BSO,can reduce the arthritis severity and decrease the mRNA expressions of IFN-γ and IL-17A in pristane-induced arthritis of rats.展开更多
基金Natural Science Foundation of Jiangsu Province(BK20180616)the Joint Funds for the Health and Education of Fujian Province(2019-WJ-31)the Institute of Respiratory Diseases,Xiamen Medical College(HXJB-15).
文摘Idiopathic pulmonary fibrosis(IPF)is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function.Chronic inflammation has been demonstrated to be the pathological basis of fibrosis.Emerging studies have revealed that most interleukin-17(IL-17)isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity.Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes,including the initiation and exacerbation of IPF.Here,we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.
基金supported by the National Natural Science Foundation of China(NO.81570675,NO.31872742)Clinical Innovation Foundation of Southwest Hospital(SWH2017JCZD-06)Top Talent Training Programme Foundation of Southwest Hospital(SWH2018BJKJ-04).
文摘Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.
基金funded by grants from the National Natural Science Foundation of China(Nos.81771761,91842304,and 81901635)Chongqing International Institute for Immunology(2020YJC10)Sanming Project of Medicine in Shenzhen(SZSM201512019)。
文摘Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear.In this study,we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A(IL-17)stimulation in SLE patients and lupus mice.Using a humanized lupus mouse model,we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs.Moreover,long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+subsets among IL-17 receptor-expressing plasma cells.Lupus mice deficient in IL-17 or IL-17 receptor C(IL-17RC)exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage,while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice.In reconstituted chimeric mice,IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells.Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization.Together,our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis,which may provide new therapeutic strategies for the treatment of SLE.
基金Project supported by the National Natural Science Foundation of China (Nos.30630058,30801027,and 30571725)the Shaanxi Province International Cooperation Foundation of China (No.2007-KW-06)
文摘Objective: This study was carried out to test the effects of methotrexate (MTX) and black seed oil (BSO) on pristane-induced arthritis (PIA) in rats.Methods: Inbred dark agouti (DA) rats were induced by a single subcutaneous injection of pristane,and then treated with MTX or BSO.Arthritis severity was evaluated macroscopically and microscopically.Plasma nitric oxide (NO) concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-time reverse transcription-polymerase chain reaction (RT-PCR).Results: The clinical arthritis severity was decreased after MTX treatment,while the BSO groups did not show significant changes compared with the disease group.The plasma NO level of the MTX group was significantly decreased compared with the disease group,but the BSO groups showed no difference from the disease group in plasma NO levels.The interferon-γ (IFN-γ) and interleukin-17A (IL-17A) mRNA expressions in the spleens were significantly decreased in the MTX group,but only showed a declining trend in the BSO groups compared with the disease group.Neither MTX nor BSO had an effect on the mRNA expressions of IL-4,transforming growth factor β (TGF-β),and tumor necrosis factor-α (TNF-α) in the spleen.Conclusions: MTX,but not BSO,can reduce the arthritis severity and decrease the mRNA expressions of IFN-γ and IL-17A in pristane-induced arthritis of rats.
