The increased incidence of systemic lupus erythematosus(SLE)in recent decades might be related to changes in modern dietary habits.Since sodium chloride(NaCl)promotes pathogenic T cell responses,we hypothesize that ex...The increased incidence of systemic lupus erythematosus(SLE)in recent decades might be related to changes in modern dietary habits.Since sodium chloride(NaCl)promotes pathogenic T cell responses,we hypothesize that excessive salt intake contributes to the increased incidence of autoimmune diseases,including SLE.Given the importance of dendritic cells(DCs)in the pathogenesis of SLE,we explored the influence of an excessive sodium chloride diet on DCs in a murine SLE model.We used an induced lupus model in which bone marrow-derived dendritic cells(BMDCs)were incubated with activated lymphocyte-derived DNA(ALD-DNA)and transferred into C57BL/6 recipient mice.We observed that a high-salt diet(HSD)markedly exacerbated lupus progression,which was accompanied by increased DC activation.NaCl treatment also stimulated the maturation,activation and antigenpresenting ability of DCs in vitro.Pretreatment of BMDCs with NaCl also exacerbated BMDC-ALD-DNA-induced lupus.These mice had increased production of autoantibodies and proinflammatory cytokines,more pronounced splenomegaly and lymphadenopathy,and enhanced pathological renal lesions.The p38 MAPK–STAT1 pathway played an important role in NaClinduced DC immune activities.Taken together,our results demonstrate that HSD intake promotes immune activation of DCs through the p38 MAPK–STAT1 signaling pathway and exacerbates the features of SLE.Thus,changes in diet may provide a novel strategy for the prevention or amelioration of lupus or other autoimmune diseases.展开更多
基金supported by the National Key R&D Program of China[2017YFA0105801]the Zhujiang Innovative and Entrepreneurial Talent Team Award of Guangdong Province[2016ZT06S252]+1 种基金the National Natural Science Foundation of China[Nos.81871224,81671611,81901657]the Natural Science Foundation of Guangdong Province[grant no.2014A030308005](all to Z.X.X.),NIH R01 AR059103,and the NIH STAR award(to S.G.Z.).
文摘The increased incidence of systemic lupus erythematosus(SLE)in recent decades might be related to changes in modern dietary habits.Since sodium chloride(NaCl)promotes pathogenic T cell responses,we hypothesize that excessive salt intake contributes to the increased incidence of autoimmune diseases,including SLE.Given the importance of dendritic cells(DCs)in the pathogenesis of SLE,we explored the influence of an excessive sodium chloride diet on DCs in a murine SLE model.We used an induced lupus model in which bone marrow-derived dendritic cells(BMDCs)were incubated with activated lymphocyte-derived DNA(ALD-DNA)and transferred into C57BL/6 recipient mice.We observed that a high-salt diet(HSD)markedly exacerbated lupus progression,which was accompanied by increased DC activation.NaCl treatment also stimulated the maturation,activation and antigenpresenting ability of DCs in vitro.Pretreatment of BMDCs with NaCl also exacerbated BMDC-ALD-DNA-induced lupus.These mice had increased production of autoantibodies and proinflammatory cytokines,more pronounced splenomegaly and lymphadenopathy,and enhanced pathological renal lesions.The p38 MAPK–STAT1 pathway played an important role in NaClinduced DC immune activities.Taken together,our results demonstrate that HSD intake promotes immune activation of DCs through the p38 MAPK–STAT1 signaling pathway and exacerbates the features of SLE.Thus,changes in diet may provide a novel strategy for the prevention or amelioration of lupus or other autoimmune diseases.
