RORγt, a novel isoform of an orphan receptor, negatively regulates Fas ligand expression and IL-2 production in T cells

RORγt, a novel isoform of an orphan receptor, negatively regulates Fas ligand expression and IL-2 production in T cells
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DOI:
10.1016/s1074-7613(00)80645-7
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发表时间:
1998-12-01
期刊:
影响因子:
32.4
通讯作者:
Bevan, MJ
Bevan, MJ
中科院分区:
医学1区
文献类型:
--
作者:
He, YW;Deftos, ML;Bevan, MJ

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我们已经鉴定了ROR γ t,一种新的胸腺特异性孤儿核受体ROR γ亚型,主要在CD 4(+)CD 8(+)双阳性胸腺细胞中表达。ROR γ t的异位表达通过抑制Pas配体的上调来保护T细胞杂交瘤免于活化诱导的细胞死亡。在杂交瘤刺激后,ROR γ t也抑制IL-2的产生,但不影响努尔-77和Egr-3的诱导,也不影响sing的上调。ROR γ t的配体结合和DNA结合结构域都是这种作用所必需的。我们提出,ROR γ t在未成熟胸腺细胞中表达的作用是抑制Pas配体表达和细胞因子分泌后,他们的TCR在积极或消极的选择。
We have identified ROR gamma t, a novel, thymus-specific isoform of the orphan nuclear receptor ROR gamma that is expressed predominantly in CD4(+) CD8(+) double-positive thymocytes. Ectopic expression of ROR gamma t protects T cell hybridomas from activation-induced cell death by inhibiting the upregulation of Pas ligand. Following hybridoma stimulation, ROR gamma t also inhibits IL-2 production but does not affect the induction of Nur-77 and Egr-3 nor the upregulation of sing. Both the ligand-binding and DNA-binding domains of ROR gamma t are required for this effect. We propose that the role of ROR gamma t expression in immature thymocytes is to inhibit Pas ligand expression and cytokine secretion following engagement of their TCR during positive or negative selection.