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PMID: 10875923 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Requirement for RORgamma in thymocyte survival and lymphoid organ development.

Science (New York, N.Y.) ·Vol. 288 ·No. 5475 ·2000-06-30 ·Pages 2369-73

Sun Z, Unutmaz D, Zou YR, Sunshine MJ, Pierani A, Brenner-Morton S, Mebius RE, Littman DR

Abstract

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.

MeSH Terms

Animals Apoptosis CDC2-CDC28 Kinases Cell Count Cell Cycle Cell Survival Crosses, Genetic Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases/metabolism DNA-Binding Proteins/genetics,metabolism Female Gene Targeting Inhibitor of Differentiation Protein 2 Lymphoid Tissue/cytology,embryology,growth & development Male Mice Mice, Inbred C57BL Nuclear Receptor Subfamily 1, Group F, Member 3 Protein Serine-Threonine Kinases/metabolism Proto-Oncogene Proteins c-bcl-2/genetics,metabolism Receptors, Cytoplasmic and Nuclear/genetics,physiology Receptors, Retinoic Acid Receptors, Thyroid Hormone Repressor Proteins T-Lymphocyte Subsets/cytology Thymus Gland/cytology Transcription Factors bcl-X Protein

Chemicals

Bcl2l1 protein, mouse DNA-Binding Proteins Idb2 protein, mouse Inhibitor of Differentiation Protein 2 Nuclear Receptor Subfamily 1, Group F, Member 3 Proto-Oncogene Proteins c-bcl-2 Receptors, Cytoplasmic and Nuclear Receptors, Retinoic Acid Receptors, Thyroid Hormone Repressor Proteins Rorc protein, mouse Transcription Factors bcl-X Protein Protein Serine-Threonine Kinases CDC2-CDC28 Kinases Cdk2 protein, mouse Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Sun 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

Zou Y R

Sunshine M J

Pierani A

Brenner-Morton S

Mebius R E

Littman D R

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.288.5475.2369

Published

2000-06-30

Pages

2369-73

Language

English

Region

United States

NLM ID

0404511

Subset

External Links

PubMed source DOI: 10.1126/science.288.5475.2369 View journal details

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Requirement for RORgamma in thymocyte survival and lymphoid organ development.

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