| First Author | Kawahara E | Year | 2022 |
| Journal | J Immunol | Volume | 208 |
| Issue | 3 | Pages | 642-650 |
| PubMed ID | 34996840 | Mgi Jnum | J:322305 |
| Mgi Id | MGI:7257941 | Doi | 10.4049/jimmunol.2001358 |
| Citation | Kawahara E, et al. (2022) TNF Receptor-Associated Factor 5 Limits IL-27 Receptor Signaling in CD4(+) T Lymphocytes. J Immunol 208(3):642-650 |
| abstractText | TNF receptor-associated factor 5 (TRAF5) restrains early signaling activity of the IL-6 receptor in naive CD4(+) T cells by interacting with the shared gp130 chain, although TRAF5 was initially discovered as a cytoplasmic adaptor protein to activate signaling mediated by TNF receptor family molecules. This leads to the question of whether TRAF5 limits signaling via the receptor for IL-27, which is composed of gp130 and WSX-1. The aim of this study is to clarify the role of TRAF5 in IL-27 receptor signaling and to understand the differential role of TRAF5 on cytokine receptor signaling. We found that Traf5 (-/-) CD4(+) T cells displayed significantly higher levels of phosphorylated STAT1 and STAT-regulated genes Socs3 and Tbx21, as early as 1 h after IL-27 exposure when compared with Traf5 (+/+) CD4(+) T cells. Upon IL-27 and TCR signals, the Traf5 deficiency significantly increased the induction of IL-10 and promoted the proliferation of CD4(+) T cells. Traf5 (-/-) mice injected with IL-27 displayed significantly enhanced delayed-type hypersensitivity responses, demonstrating that TRAF5 works as a negative regulator for IL-27 receptor signaling. In contrast, IL-2 and proliferation mediated by glucocorticoid-induced TNF receptor-related protein (GITR) and TCR signals were significantly decreased in Traf5 (-/-) CD4(+) T cells, confirming that TRAF5 works as a positive regulator for cosignaling via GITR. Collectively, our results demonstrate that TRAF5 reciprocally controls signals mediated by the IL-27 receptor and GITR in CD4(+) T cells and suggest that the regulatory activity of TRAF5 in gp130 is distinct from that in TNF receptor family molecules in a T cell. |
