Help Privacy Policy Disclaimer
  Advanced SearchBrowse




Journal Article

TRAF6 inhibits Th17 differentiation and TGF-beta-mediated suppression of IL-2


Pearce,  Erika L.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)

Cejes et al..pdf
(Publisher version), 767KB

Supplementary Material (public)
There is no public supplementary material available

Cejas, P. J., Walsh, M. C., Pearce, E. L., Han, D., Harms, G. M., Artis, D., et al. (2012). TRAF6 inhibits Th17 differentiation and TGF-beta-mediated suppression of IL-2. Blood, 115, 4750-4757. doi:10.1182/blood-2009-09-242768.

Cite as: https://hdl.handle.net/21.11116/0000-0006-612A-E
Transforming growth factor-β (TGF-β) 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-β–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-β–induced Smad2/3 activation and proliferation arrest. Consistent with this, in TRAF6-deficient T cells, TGF-β 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-β signaling and Th17 differentiation. Importantly, the data also suggest that a main function of TGF-β in early Th17 differentiation may be the inhibition of autocrine and paracrine IL-2–mediated suppression of Th17 cell generation.