Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to...Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to regulating the proliferation,differentiation,and migration of Th17 and Treg cells.Wdr63,a gene containing the WD repeat domain,participates in the structure and functional modulation of actin cytoskeleton.Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition.This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis.Methods We constructed Wdr63-/-mice,induced colitis in mice using dextran sulfate sodium salt,collected colon tissue for histopathological staining,collected mesenteric lymph nodes for flow cytometry analysis,and collected healthy mouse feces for microbial diversity detection.Results Compared with wild-type colitis mice,Wdr63-/-colitis mice had a more pronounced shortening of colonic tissue,higher scores on disease activity index and histological damage index,Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes,a lower level of anti-inflammatory cytokine IL-10,and a higher level of pro-inflammatory cytokine IL-17A.In addition,WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis.It maintains the balance of Bacteroidota and Firmicutes,promoting the formation of beneficial intestinal bacteria linked to immune inflammation.Conclusion Wdr63 deletion aggravates ulcerative colitis in mice,WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.展开更多
Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sam...Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.展开更多
文摘Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to regulating the proliferation,differentiation,and migration of Th17 and Treg cells.Wdr63,a gene containing the WD repeat domain,participates in the structure and functional modulation of actin cytoskeleton.Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition.This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis.Methods We constructed Wdr63-/-mice,induced colitis in mice using dextran sulfate sodium salt,collected colon tissue for histopathological staining,collected mesenteric lymph nodes for flow cytometry analysis,and collected healthy mouse feces for microbial diversity detection.Results Compared with wild-type colitis mice,Wdr63-/-colitis mice had a more pronounced shortening of colonic tissue,higher scores on disease activity index and histological damage index,Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes,a lower level of anti-inflammatory cytokine IL-10,and a higher level of pro-inflammatory cytokine IL-17A.In addition,WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis.It maintains the balance of Bacteroidota and Firmicutes,promoting the formation of beneficial intestinal bacteria linked to immune inflammation.Conclusion Wdr63 deletion aggravates ulcerative colitis in mice,WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.
基金This work was supported by the National Natural Science Foundation (82273506,82273508)the Hunan Provincial Health Commission Scientific Research Plan Project (D202304128334),China。
文摘Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.
