Requirement for RORγ in Thymocyte Survival and Lymphoid Organ Development

• Published in: Science (American Association for the Advancement of Science) 2000-06, Vol.288 (5475), p.2369-2373
• Main Authors: Sun, Zuoming, Unutmaz, Derya, Zou, Yong-Rui, Sunshine, Mary Jean, Pierani, Alessandra, Brenner-Morton, Susan, Mebius, Reina E., Littman, Dan R.
• Format: Article
• Language: English
• Subjects: Apoptosis; B lymphocytes; Bcl-xL protein; Biological and medical sciences; Cell cycle; Cells; Embryonic stem cells; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression regulation; Immunobiology; Lymph nodes; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; nuclear hormone receptors; ROR^g protein; Stem cells; T lymphocytes; Thymocytes
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.288.5475.2369

Most developing thymocytes undergo apoptosis because they cannot interact productively with molecules encoded by the major histocompatibility complex. Here, we show that mice lacking the orphan nuclear hormone receptor RORγ lose thymic expression of the anti-apoptotic factor Bcl-xL. RORγ thus regulates the survival of CD4+8+thymocytes and may control the temporal window during which thymocytes can undergo positive selection. RORγ was also required for development of lymph nodes and Peyer's patches, but not splenic follicles. In its absence, there was loss of a population of CD3-CD4+CD45+cells that normally express RORγ and that are likely early progenitors of lymphoid organs. Hence, RORγ has critical functions in T cell repertoire selection and lymphoid organogenesis.