RORgamma t, a novel isoform of an orphan receptor, negatively regulates Fas ligand expression and IL-2 production in T cells.
We have identified RORgamma t, a novel, thymus-specific isoform of the orphan nuclear receptor RORgamma that is expressed predominantly in CD4+ CD8+ double-positive thymocytes. Ectopic expression of RORgamma t protects T cell hybridomas from activation-induced cell death by inhibiting the upregulation of Fas ligand. Following hybridoma stimulation, RORgamma t also inhibits IL-2 production but does not affect the induction of Nur-77 and Egr-3 nor the upregulation of CD69. Both the ligand-binding and DNA-binding domains of RORgamma t are required for this effect. We propose that the role of RORgamma t expression in immature thymocytes is to inhibit Fas ligand expression and cytokine secretion following engagement of their TCR during positive or negative selection.
He
Y W
YW
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.
Deftos
M L
ML
Ojala
E W
EW
Bevan
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D053222:Fas Ligand Protein; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006825:Hybridomas; D007376:Interleukin-2 / Q000096:biosynthesis*; D007739:L Cells; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse