The role of orphan nuclear receptor in thymocyte differentiation and lymphoid organ development.
T lymphocytes differentiate in the thymus through several phenotypically distinct stages that are tightly regulated by multiple nuclear transcription factors. Immature CD4+CD8+ double positive (DP) thymocytes make up a majority of the population in the thymus, and exhibit several phenotypic features distinct from mature T cells. DP thymocytes express only about 10% of surface TCR that are found on mature T cells and do not proliferate and produce IL-2 in response to stimulation. Several critical events of T lymphocyte maturation such as TCRalpha gene recombination, positive and negative selection, and CD4/CD8 lineage commitment occur around the DP stage. Recent studies from our group and others on the orphan nuclear receptor RORgamma and its thymus-specific isoform RORgammat support a critical role for this nuclear receptor in the regulation of DP thymocyte function. In addition, RORgamma is required for the development of lymph nodes and Peyer's patches.
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Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D006801:Humans; D008198:Lymph Nodes / Q000254:growth & development*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010581:Peyer's Patches / Q000254:growth & development*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*; D014158:Transcription, Genetic
D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone