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

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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570 Biowissenschaften, Biologie

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SEITZ, Carina, Svenja MICHALEK, Truong San PHAN, Cindy REINHOLD, Lea DIETRICH, Christian SCHMIDT, M. Eugenia DELGADO, Theresa SCHNALZGER, Thomas BRUNNER, 2019. The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions. In: Science advances. 2019, 5(7), eaav9732. eISSN 2375-2548. Available under: doi: 10.1126/sciadv.aav9732

BibTex

@article{Seitz2019-07orpha-46502,
  year={2019},
  doi={10.1126/sciadv.aav9732},
  title={The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions},
  number={7},
  volume={5},
  journal={Science advances},
  author={Seitz, Carina and Michalek, Svenja and Phan, Truong San and Reinhold, Cindy and Dietrich, Lea and Schmidt, Christian and Delgado, M. Eugenia and Schnalzger, Theresa and Brunner, Thomas},
  note={Article Number: eaav9732}
}

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