Local synthesis of immunosuppressive glucocorticoids in the intestinal epithelium regulates anti-viral immune responses

Cellular Immunology
Juan HuangThomas Brunner

Abstract

The nuclear receptor Small Heterodimer Partner (SHP) is a transcriptional target and inhibitor of Liver Receptor Homolog 1 (LRH-1), the transcriptional regulator of intestinal glucocorticoid (GC) synthesis. The role of SHP in the regulation of intestinal GC synthesis and its impact on T cell-mediated anti-viral immune responses in the intestinal mucosa are currently not understood. Lymphocytic choriomeningitis virus (LCMV) infection promoted intestinal GC synthesis, which was enhanced in SHP-deficient mice. Intestinal GC suppressed the expansion and altered the activation of virus-specific T cells. In contrast, deletion of LRH-1 reduced intestinal GC synthesis and accelerated the expansion of cytotoxic T cells post LCMV infection. These findings show that virus-induced intestinal GC synthesis is controlled by LRH-1 and SHP, and that local steroidogenesis contributes to the maintenance of intestinal immune homeostasis. Thus, LRH-1-regulated intestinal GC synthesis could represent an interesting therapeutic target in the treatment of inflammatory disorders.

Citations

Jan 29, 2019·Genes and Immunity·M Eugenia Delgado, Thomas Brunner
Jul 25, 2019·Frontiers in Immunology·Steven TimmermansClaude Libert
Jan 30, 2019·Genes and Immunity·Truong San PhanThomas Brunner
Mar 31, 2021·Molecular and Cellular Endocrinology·Jianguo WuLi Wang
May 1, 2021·International Journal of Molecular Sciences·Peter ErgangJiří Pácha

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