Vitamin D3 receptor polymorphisms regulate T cells and T cell-dependent inflammatory diseases

Lahore Gonzalo Fernandez; Raposo Bruno; Lagerquist MarieOhlsson ClaesSabatier PierreXu BingzeAoun MikeJames JaimeCai XiaojieZubarev Roman A.Nandakumar Kutty SelvaHolmdahl Rikard

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Vitamin D3 receptor polymorphisms regulate T cells and T cell-dependent inflammatory diseases

机译：Vitamin D3 receptor polymorphisms regulate T cells and T cell-dependent inflammatory diseases

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It has proven difficult to identify the underlying genes in complex autoimmune diseases. Here, we use forward genetics to identify polymorphisms in the vitamin D receptor gene (Vdr) promoter, controlling Vdr expression and T cell activation. We isolated these polymorphisms in a congenic mouse line, allowing us to study the immunomodulatory properties of VDR in a physiological context. Congenic mice overexpressed VDR selectively in T cells, and thus did not suffer from calcemic effects. VDR overexpression resulted in an enhanced antigen-specific T cell response and more severe autoimmune phenotypes. In contrast, vitamin D3-deficiency inhibited T cell responses and protected mice from developing autoimmune arthritis. Our observations are likely translatable to humans, as Vdr is overexpressed in rheumatic joints. Genetic control of VDR availability codetermines the proinflammatory behavior of T cells, suggesting that increased presence of VDR at the site of inflammation might limit the antiinflammatory properties of its ligand.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2020年第40期|24986-24997|共12页
作者
Lahore Gonzalo Fernandez; Raposo Bruno; Lagerquist MarieOhlsson ClaesSabatier PierreXu BingzeAoun MikeJames JaimeCai XiaojieZubarev Roman A.Nandakumar Kutty SelvaHolmdahl Rikard;
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作者单位

Dept Med Biochem & Biophys,Karolinska Inst;

Ctr Bone & Arthrit Res,Univ Gothenburg;

Dept Pharmacol & Technol Chem,IM Sechenov First Moscow State Med Univ;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
vitamin D receptor; vitamin D; inflammation; T cells; genetics; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; COLLAGEN-INDUCED ARTHRITIS; 1; 25-DIHYDROXYVITAMIN D-3; RHEUMATOID-ARTHRITIS; GENE-EXPRESSION; DENDRITIC CELLS; INDUCED COLITIS; IMMUNE-SYSTEM; II COLLAGEN; SUSCEPTIBILITY;

Vitamin D3 receptor polymorphisms regulate T cells and T cell-dependent inflammatory diseases

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