LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease. - Archive ouverte HAL Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2007

LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease.

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Abstract

Liver receptor homolog-1 (LRH-1) is a nuclear receptor involved in intestinal lipid homeostasis and cell proliferation. Here we show that haploinsufficiency of LRH-1 predisposes mice to the development of intestinal inflammation. Besides the increased inflammatory response, LRH-1 heterozygous mice exposed to 2,4,6-trinitrobenzene sulfonic acid show lower local corticosterone production as a result of an impaired intestinal expression of the enzymes CYP11A1 and CYP11B1, which control the local synthesis of corticosterone in the intestine. Local glucocorticoid production is strictly enterocyte-dependent because it is robustly reduced in epithelium-specific LRH-1-deficient mice. Consistent with these findings, colon biopsies of patients with Crohn's disease and ulcerative colitis show reduced expression of LRH-1 and genes involved in the production of glucocorticoids. Hence, LRH-1 regulates intestinal immunity in response to immunological stress by triggering local glucocorticoid production. These findings underscore the importance of LRH-1 in the control of intestinal inflammation and the pathogenesis of inflammatory bowel disease.

Dates and versions

hal-00189378 , version 1 (20-11-2007)

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Agnès Coste, Laurent Dubuquoy, Romain Barnouin, Jean-Sébastien Annicotte, Benjamin Magnier, et al.. LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease.. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104 (32), pp.13098-103. ⟨10.1073/pnas.0702440104⟩. ⟨hal-00189378⟩
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