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
Depression poses a considerable threat to global health,underscoring the critical need for safe treatments.Because of its homology of medicine and food,Gardeniae Fructus is widely used in clinical and everyday life co...Depression poses a considerable threat to global health,underscoring the critical need for safe treatments.Because of its homology of medicine and food,Gardeniae Fructus is widely used in clinical and everyday life contexts.Gardeniae Fructus oil(OGF)is a waste byproduct of the food industry with promising recycling potential.While previous research has demonstrated the antidepressant effects of OGF,the precise mechanism remains unclear.To fill this gap in the literature,this paper elucidates the composition and potential antidepressant mechanism of OGF.According to the results,OGF is mainly composed of fatty acids and unsaponifiable matter.OGF could effectively attenuate depression-like behaviors in mice with chronic unpredictable mild stress by modulating the microbiota-gut-brain axis.Mechanisms include improving gut dysbiosis,regulating short-chain fatty acids,protecting the intestinal barrier function,reducing hippocampal damage,and alleviating neuroinflammation by inhibiting the activation of the TLR4/NF-κB/NLRP3 pathway.Fecal microbiota transplantation experiments confirmed the involvement of the gut microbiota in the modulation of depression-like behavior by OGF.This study establishes the antidepressant effects of OGF as well as the underlying mechanism,demonstrating its potential as a novel dietary intervention for depression treatment.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
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
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
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supported by the Natural Science Foundation of Hubei Province(2024AFD225)the Major Task Innovation Project of Hubei Province(2023BEB011)+1 种基金the Natural Science Foundation of Hubei Province(2023AFB403)the Central Guided Local Science and Technology Development Special Project of Hubei Province(2019ZYYD069)。
文摘Depression poses a considerable threat to global health,underscoring the critical need for safe treatments.Because of its homology of medicine and food,Gardeniae Fructus is widely used in clinical and everyday life contexts.Gardeniae Fructus oil(OGF)is a waste byproduct of the food industry with promising recycling potential.While previous research has demonstrated the antidepressant effects of OGF,the precise mechanism remains unclear.To fill this gap in the literature,this paper elucidates the composition and potential antidepressant mechanism of OGF.According to the results,OGF is mainly composed of fatty acids and unsaponifiable matter.OGF could effectively attenuate depression-like behaviors in mice with chronic unpredictable mild stress by modulating the microbiota-gut-brain axis.Mechanisms include improving gut dysbiosis,regulating short-chain fatty acids,protecting the intestinal barrier function,reducing hippocampal damage,and alleviating neuroinflammation by inhibiting the activation of the TLR4/NF-κB/NLRP3 pathway.Fecal microbiota transplantation experiments confirmed the involvement of the gut microbiota in the modulation of depression-like behavior by OGF.This study establishes the antidepressant effects of OGF as well as the underlying mechanism,demonstrating its potential as a novel dietary intervention for depression treatment.
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.
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.
