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Vitamin D receptor is required to control gastrointestinal immunity in IL‐10 knockout mice
Author(s) -
Froicu Monica,
Zhu Yan,
Cantorna Margherita T.
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2005.02290.x
Subject(s) - calcitriol receptor , inflammation , immune system , mesenteric lymph nodes , biology , endocrinology , medicine , spleen , knockout mouse , gastrointestinal tract , tumor necrosis factor alpha , receptor , immunology , vitamin d and neurology
Summary The vitamin D receptor (VDR) is a nuclear receptor expressed in a number of different cells of the immune system. This study was performed to determine the effect of VDR deficiency on immune function and inflammation of the gastrointestinal tract in a model of inflammatory bowel disease, namely interleukin‐10 (IL‐10) knockout mice. IL‐10 knockout mice were generated which either could or could not respond to vitamin D (double IL‐10/VDR knockout; DKO). The distribution and function of lymphocytes in both the primary and secondary lymphoid organs were compared and determined as a function of the severity of intestinal inflammation. DKO mice had normal thymic development and peripheral T‐cell numbers at 3 weeks of age, but a week after intestinal disease was detected the thymus was dysplastic with a reduction in cellularity. The atrophy was coupled with increased apoptosis. The spleen weight of DKO mice increased as a result of the accumulation of red blood cells; however, there was a 50% reduction in the numbers of T and B cells. Conversely, the mesenteric lymph nodes were enlarged and contained increased numbers of lymphocytes. The T cells from DKO mice were of a memory phenotype and were hyporesponsive to T‐cell receptor stimulation. Colitis in the DKO mice was associated with local and high expression of IL‐2, interferon‐γ, IL‐1β, tumour necrosis factor‐α and IL‐12. The primary and secondary lymphoid organs in DKO mice are profoundly altered as a consequence of the fulminating inflammation in the gastrointestinal tract. VDR expression is required for the T cells and other immune cells to control inflammation in the IL‐10 KO mice.