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Science 288 (5475): 2369-2373

Copyright © 2000 by the American Association for the Advancement of Science

Requirement for RORgamma in Thymocyte Survival and Lymphoid Organ Development

Zuoming Sun, 1 Derya Unutmaz, 1 Yong-Rui Zou, 1 Mary Jean Sunshine, 12 Alessandra Pierani, 3 Susan Brenner-Morton, 34 Reina E. Mebius, 5 Dan R. Littman 12*

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.

1 Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine and
2 Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.
3 Department of Biochemistry and Molecular Biophysics and
4 Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
5 Faculty of Medicine, Department of Cell Biology and Immunology, Vrije Universiteit, 1081 BT Amsterdam, Netherlands.
*   To whom correspondence should be addressed. E-mail: littman{at}

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E. Ueda, S. Kurebayashi, M. Sakaue, M. Backlund, B. Koller, and A. M. Jetten (2002)
Cancer Res. 62, 901-909
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Cutting Edge: Organogenesis of Nasal-Associated Lymphoid Tissue (NALT) Occurs Independently of Lymphotoxin-{alpha} (LT{alpha}) and Retinoic Acid Receptor-Related Orphan Receptor-{gamma}, but the Organization of NALT Is LT{alpha} Dependent.
A. Harmsen, K. Kusser, L. Hartson, M. Tighe, M. J. Sunshine, J. D. Sedgwick, Y. Choi, D. R. Littman, and T. D. Randall (2002)
J. Immunol. 168, 986-990
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Requirement for the NF-{kappa}B Family Member RelA in the Development of Secondary Lymphoid Organs.
E. Alcamo, N. Hacohen, L. C. Schulte, P. D. Rennert, R. O. Hynes, and D. Baltimore (2002)
J. Exp. Med. 195, 233-244
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The Fetal Liver Counterpart of Adult Common Lymphoid Progenitors Gives Rise to All Lymphoid Lineages, CD45+CD4+CD3- Cells, As Well As Macrophages.
R. E. Mebius, T. Miyamoto, J. Christensen, J. Domen, T. Cupedo, I. L. Weissman, and K. Akashi (2001)
J. Immunol. 166, 6593-6601
   Abstract »    Full Text »    PDF »
Lymphoid neogenesis: de novo formation of lymphoid tissue in chronic inflammation through expression of homing chemokines.
P. Hjelmstrom (2001)
J. Leukoc. Biol. 69, 331-339
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