Requirement for RORgamma in thymocyte survival and lymphoid organ development.
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 RORgamma lose thymic expression of the anti-apoptotic factor Bcl-xL. RORgamma thus regulates the survival of CD4+8+ thymocytes and may control the temporal window during which thymocytes can undergo positive selection. RORgamma 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 RORgamma and that are likely early progenitors of lymphoid organs. Hence, RORgamma has critical functions in T cell repertoire selection and lymphoid organogenesis.
Sun
Z
Z
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine and Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.
Unutmaz
D
D
Zou
Y R
YR
Sunshine
M J
MJ
Pierani
A
A
Brenner-Morton
S
S
Mebius
R E
RE
Littman
D R
DR
D000818:Animals; D017209:Apoptosis; D042846:CDC2-CDC28 Kinases; D002452:Cell Count; D002453:Cell Cycle; D002470:Cell Survival; D003433:Crosses, Genetic; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D051797:Inhibitor of Differentiation Protein 2; D008221:Lymphoid Tissue / Q000166:cytology / Q000196:embryology / Q000254:growth & development*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology*; D014157:Transcription Factors; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D004268:DNA-Binding Proteins; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D019253:Proto-Oncogene Proteins c-bcl-2; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; C539901:Rorc protein, mouse; D014157:Transcription Factors; D051020:bcl-X Protein; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases