| First Author | Chan CT | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 10 | PubMed ID | 32716519 |
| Mgi Jnum | J:298710 | Mgi Id | MGI:6477213 |
| Doi | 10.1084/jem.20200318 | Citation | Chan CT, et al. (2020) Liver X receptors are required for thymic resilience and T cell output. J Exp Med 217(10) |
| abstractText | The thymus is a primary lymphoid organ necessary for optimal T cell development. Here, we show that liver X receptors (LXRs)-a class of nuclear receptors and transcription factors with diverse functions in metabolism and immunity-critically contribute to thymic integrity and function. LXRalphabeta-deficient mice develop a fatty, rapidly involuting thymus and acquire a shrunken and prematurely immunoinhibitory peripheral T cell repertoire. LXRalphabeta's functions are cell specific, and the resulting phenotypes are mutually independent. Although thymic macrophages require LXRalphabeta for cholesterol efflux, thymic epithelial cells (TECs) use LXRalphabeta for self-renewal and thymocytes for negative selection. Consequently, TEC-derived LXRalphabeta protects against homeostatic premature involution and orchestrates thymic regeneration following stress, while thymocyte-derived LXRalphabeta limits cell disposal during negative selection and confers heightened sensitivity to experimental autoimmune encephalomyelitis. These results identify three distinct but complementary mechanisms by which LXRalphabeta governs T lymphocyte education and illuminate LXRalphabeta's indispensable roles in adaptive immunity. |
