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Abstract
Crohn’s disease (CD) and ulcerative colitis (UC) actually had different pathological mechanisms, as the former was mainly induced by Th1 and Th17 response and the latter by Th2 response. Our previous study found that oxazolone-induced Th2-mediated colitis could not be attenuated by vitamin D supplementation. This study investigated the influence of intestinal vitamin D receptor (VDR) knockout on oxazolone-induced colitis and explored the possible immunological mechanism. Intestinal VDR knockout mice had milder oxazolone-induced colitis than wildtype controls, as demonstrated by less body weight decrease and faster recovery, more intact local structure, reduced cell apoptosis, and better preserved barrier function. Th2-mediated inflammation was significantly inhibited by VDR deficiency. Meanwhile, the percentage of invariant natural killer T (iNKT) cells did not increase as much in intestinal VDR knockout mice as in wild-type controls, nor did the iNKT cells develop normally as in the controls. Intestinal VDR knockout protected against oxazolone-induced colitis in mice by blocking Th2 cell response and reducing the function of intestinal iNKT cells. Vitamin D status had no influence on the severity of colitis. This study may explain the diverse outcomes after vitamin D supplementation in literature and add some clue to the targeted therapy of IBD.
Highlights
Introduction VitaminD deficiency had been closely associated with auto-immunological diseases including IBD
Wild-type mice challenged by oxazolone (WT OX) presented with significant body weight loss in the first three days and 9/32 mice died
Intestinal vitamin D knockout challenged by oxazolone (KO OX) showed very mild colitis changes
Summary
Introduction VitaminD deficiency had been closely associated with auto-immunological diseases including IBD. Dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS) were frequently used to induce Th1/ Th17-associated colitis that represented the Crohn’s disease, while oxazolone was used to simulate ulcerative colitis by inducing Th2 inflammatory response. Immunological defect models, such as IL-10 knockout and sensitized Rag models had spontaneous colitis due to complicated imuno-pathological mechanisms[6]. While in those VDR global knockout mice with intestinal-specific human VDR knock-in, the colitis would be significantly inhibited[9] This was probably due to the suppressive effect of vitamin D signaling pathway on Th1 andTh17 cell response
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