PLX269694

GSE144342: Thymic resilience and T cell output require Liver X Receptors

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

The thymus is a primary lymphoid organ necessary for optimal T cell development. Here we show that liver X receptors, which are a class of nuclear receptors and transcription factors with diverse functions in metabolism and immunity, critically contribute to thymic integrity and function. LXR-deficient mice develop a fatty, rapidly-involuting thymus, and acquire a shrunken and prematurely senescent peripheral T cell repertoire. The functions of LXR are cell specific and the resulting phenotypes mutually independent. Whereas macrophages require LXR for reverse cholesterol transport and lipid removal, thymic epithelial cells (TEC) and thymocytes respectively utilize LXR for self-renewal and negative selection. Consequently, TEC-derived LXR protect against premature involution in homeostasis and orchestrate thymic regeneration following stress, while thymocyte-derived LXR limit cell disposal during negative selection and confer heightened sensitivity to experimental autoimmune encephalomyelitis. These results identify three distinct but complementary mechanisms by which LXR govern T lymphocyte education. SOURCE: Christopher Chan Massachusetts General Hospital