Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice ...Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.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
Follicular helper T (Tfh) cells play a key role in driving B cell activation and differentiation during germinal center reactions in immune responses and autoimmune development, and these cells are characterized by hi...Follicular helper T (Tfh) cells play a key role in driving B cell activation and differentiation during germinal center reactions in immune responses and autoimmune development, and these cells are characterized by high expression of CXCR5, PD1, ICOS, IL-21 and BCL6. Increasing evidence indicates that the functional dysregulation of Tfh cells contributes to the pathogenesis of autoimmune diseases, including primary Sjögren’s syndrome (pSS), which is a common autoimmune disease characterized by lymphocytic infiltration and tissue inflammation in salivary glands (SGs) and lacrimal glands that leads to dry mouth and dry eyes.1 Here, we provide a brief commentary on recent advances in understanding the Tfh cell response with a focus on new insights into Tfh cell regulation and therapeutic implications in autoimmune diseases.展开更多
To the Editor:Psoriatic arthritis(PsA)is a chronic inflammatory musculoskeletal disease associated with psoriasis,mainly manifested as peripheral arthritis,enthesitis,finger or toe inflammation,and spinal arthritis.[1...To the Editor:Psoriatic arthritis(PsA)is a chronic inflammatory musculoskeletal disease associated with psoriasis,mainly manifested as peripheral arthritis,enthesitis,finger or toe inflammation,and spinal arthritis.[1]PsA may develop at any age,peaking at age of 30 to 50 years with no significant gender difference,but the spinal involvement is more frequent in men.The prevalence of PsA in China is about 1.23‰.About 75%of patients with PsA develop rash before arthritic onset whereas 10%after arthritis development.展开更多
Dear Editor,Primary Sjogren's syndrome(pSS)is an autoimmune disease characterized by dry eyes and dry mouth caused by glandular inflammation in salivary glands(SG)and lacrimal glands.Currently,pSS patients are suf...Dear Editor,Primary Sjogren's syndrome(pSS)is an autoimmune disease characterized by dry eyes and dry mouth caused by glandular inflammation in salivary glands(SG)and lacrimal glands.Currently,pSS patients are suffering from a lack of effective therapies.Many studies have revealed dysregulated immune responses during pSS development,in which Th17 cells are considered as the key driver in disease initiation and perpetuation.展开更多
基金supported financially by the National Natural Science Foundation of China,No.82071272(to YZ).
文摘Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.
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supported by grants from the National Natural Science Foundation of China(Nos.82071817 and 82004171)the Chongqing International Institute for Immunology(2020YJC10)+3 种基金the Hong Kong Research Grants Council(17149716)Fundamental Research Funds for Central Public Welfare Research Institutes(ZZ13-YQ-033-C1)the Young Elite Scientist Sponsorship Program of CACM(CACM-2020-QNRC2-05)HKU Seed Funding for Strategic Interdisciplinary Research Scheme.
文摘Follicular helper T (Tfh) cells play a key role in driving B cell activation and differentiation during germinal center reactions in immune responses and autoimmune development, and these cells are characterized by high expression of CXCR5, PD1, ICOS, IL-21 and BCL6. Increasing evidence indicates that the functional dysregulation of Tfh cells contributes to the pathogenesis of autoimmune diseases, including primary Sjögren’s syndrome (pSS), which is a common autoimmune disease characterized by lymphocytic infiltration and tissue inflammation in salivary glands (SGs) and lacrimal glands that leads to dry mouth and dry eyes.1 Here, we provide a brief commentary on recent advances in understanding the Tfh cell response with a focus on new insights into Tfh cell regulation and therapeutic implications in autoimmune diseases.
文摘To the Editor:Psoriatic arthritis(PsA)is a chronic inflammatory musculoskeletal disease associated with psoriasis,mainly manifested as peripheral arthritis,enthesitis,finger or toe inflammation,and spinal arthritis.[1]PsA may develop at any age,peaking at age of 30 to 50 years with no significant gender difference,but the spinal involvement is more frequent in men.The prevalence of PsA in China is about 1.23‰.About 75%of patients with PsA develop rash before arthritic onset whereas 10%after arthritis development.
基金This work was supported by Chongqing International Institute for Immunology(2020YJC10)National Natural Science Foundation of China(82071817,82171771,82004171,81971542)+4 种基金Shenzhen Science and Technology Program(YCYJ20210324114602008)Young Elite Scientist Sponsorship Program by CACM(CACM-2020-QNRC2-05)Hong Kong Research Grants Council(17113319,17103821)RGC Theme-based Research Scheme(TRS)(T12-703/19-R)the Centre for Oncology and Immunology under the Health@InnoHK Initiative funded by the Innovation and Technology Commission,The Government of Hong Kong SAR,China.
文摘Dear Editor,Primary Sjogren's syndrome(pSS)is an autoimmune disease characterized by dry eyes and dry mouth caused by glandular inflammation in salivary glands(SG)and lacrimal glands.Currently,pSS patients are suffering from a lack of effective therapies.Many studies have revealed dysregulated immune responses during pSS development,in which Th17 cells are considered as the key driver in disease initiation and perpetuation.
