| First Author | Cejas PJ | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 23 | Pages | 4750-7 |
| PubMed ID | 20351308 | Mgi Jnum | J:161549 |
| Mgi Id | MGI:4459600 | Doi | 10.1182/blood-2009-09-242768 |
| Citation | Cejas PJ, et al. (2010) TRAF6 inhibits Th17 differentiation and TGF-beta-mediated suppression of IL-2. Blood 115(23):4750-7 |
| abstractText | Transforming growth factor-beta (TGF-beta) has an essential role in the generation of inducible regulatory T (iTreg) and T helper 17 (Th17) cells. However, little is known about the TGF-beta-triggered pathways that drive the early differentiation of these cell populations. Here, we report that CD4(+) T cells lacking the molecular adaptor tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) exhibit a specific increase in Th17 differentiation in vivo and in vitro. We show that TRAF6 deficiency renders T cells more sensitive to TGF-beta-induced Smad2/3 activation and proliferation arrest. Consistent with this, in TRAF6-deficient T cells, TGF-beta more effectively down-regulates interleukin-2 (IL-2), a known inhibitor of Th17 differentiation. Remarkably, TRAF6-deficient cells generate normal numbers of Foxp3-expressing cells in iTreg differentiation conditions where exogenous IL-2 is supplied. These findings show an unexpected role for the adaptor molecule TRAF6 in Smad-mediated TGF-beta signaling and Th17 differentiation. Importantly, the data also suggest that a main function of TGF-beta in early Th17 differentiation may be the inhibition of autocrine and paracrine IL-2-mediated suppression of Th17 cell generation. |
