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Publication : The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions.

First Author  Seitz C Year  2019
Journal  Sci Adv Volume  5
Issue  7 Pages  eaav9732
PubMed ID  31328159 Mgi Jnum  J:288687
Mgi Id  MGI:6429997 Doi  10.1126/sciadv.aav9732
Citation  Seitz C, et al. (2019) The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions. Sci Adv 5(7):eaav9732
abstractText  LRH-1 (liver receptor homolog-1/NR5a2) is an orphan nuclear receptor, which regulates glucose and lipid metabolism, as well as intestinal inflammation via the transcriptional control of intestinal glucocorticoid synthesis. Predominantly expressed in epithelial cells, its expression and role in immune cells are presently enigmatic. LRH-1 was found to be induced in immature and mature T lymphocytes upon stimulation. T cell-specific deletion of LRH-1 causes a drastic loss of mature peripheral T cells. LRH-1-depleted CD4(+) T cells exert strongly reduced activation-induced proliferation in vitro and in vivo and fail to mount immune responses against model antigens and to induce experimental intestinal inflammation. Similarly, LRH-1-deficient cytotoxic CD8(+) T cells fail to control viral infections. This study describes a novel and critical role of LRH-1 in T cell maturation, functions, and immopathologies and proposes LRH-1 as an emerging pharmacological target in the treatment of T cell-mediated inflammatory diseases.
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