Lymphocyte accumulation in the spleen of retinoic acid receptor-related orphan receptor gamma-deficient mice.
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.
Zhang
Nu
N
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Guo
Jian
J
He
You-Wen
YW
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics* / Q000276:immunology*; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D007399:Interphase / Q000235:genetics / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011828:Radiation Chimera / Q000276:immunology; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D013154:Spleen / Q000033:anatomy & histology / Q000166:cytology* / Q000276:immunology*; D013163:Splenomegaly / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse