Abstract
The hormone nuclear receptor retinoic acid receptor-related orphan receptor gamma (RORgamma) plays important roles in thymocyte development and lymphoid organogenesis. RORgamma and its thymus-specific isoform RORgammat are expressed in the thymus, but not in the spleen and bone marrow (BM). However, RORgamma(-/-) mice have 2- to 3-fold more splenocytes than wild-type controls due to an accumulation of conventional resting B lymphocytes. The increase in B lymphocytes in RORgamma(-/-) mice is caused neither by abnormal B cell development in the BM nor by an obvious defect in the peripheral T cell compartment. Furthermore, analyses of BM chimeras using either RORgamma(-/-) or recombinase-activating gene-2(-/-) mice as recipients and wild-type or RORgamma(-/-) mice as donors, respectively, demonstrate that the splenic microenvironment of RORgamma(-/-) mice is defective, since wild-type T and B lymphocytes accumulated in these chimeric mice. In addition, T lymphocyte homeostasis was altered due to a lowered thymic output in RORgamma(-/-) mice. Collectively, these results suggest that RORgamma regulates lymphocyte homeostasis at multiple levels.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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B-Lymphocyte Subsets / cytology
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / metabolism
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Bone Marrow Transplantation / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Movement / genetics*
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Cell Movement / immunology*
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Homeostasis / genetics
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Homeostasis / immunology
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Immunophenotyping
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Interphase / genetics
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Interphase / immunology
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Lymphocyte Subsets / cytology*
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Lymphocyte Subsets / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Radiation Chimera / immunology
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Receptors, Cytoplasmic and Nuclear / deficiency*
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Receptors, Cytoplasmic and Nuclear / genetics*
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Receptors, Cytoplasmic and Nuclear / physiology
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Receptors, Retinoic Acid*
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Receptors, Thyroid Hormone*
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Spleen / anatomy & histology
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Spleen / cytology*
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Spleen / immunology*
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Splenomegaly / genetics
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Splenomegaly / immunology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
Substances
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Rorc protein, mouse