| First Author | Ghoreschi K | Year | 2010 |
| Journal | Nature | Volume | 467 |
| Issue | 7318 | Pages | 967-71 |
| PubMed ID | 20962846 | Mgi Jnum | J:165551 |
| Mgi Id | MGI:4837752 | Doi | 10.1038/nature09447 |
| Citation | Ghoreschi K, et al. (2010) Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 467(7318):967-71 |
| abstractText | CD4(+) T-helper cells that selectively produce interleukin (IL)-17 (T(H)17), are critical for host defence and autoimmunity. Although crucial for T(H)17 cells in vivo, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-beta1 have been proposed to be the factors responsible for initiating specification. Here we show that T(H)17 differentiation can occur in the absence of TGF-beta signalling. Neither IL-6 nor IL-23 alone efficiently generated T(H)17 cells; however, these cytokines in combination with IL-1beta effectively induced IL-17 production in naive precursors, independently of TGF-beta. Epigenetic modification of the Il17a, Il17f and Rorc promoters proceeded without TGF-beta1, allowing the generation of cells that co-expressed RORgammat (encoded by Rorc) and T-bet. T-bet(+)RORgammat(+) T(H)17 cells are generated in vivo during experimental allergic encephalomyelitis, and adoptively transferred T(H)17 cells generated with IL-23 without TGF-beta1 were pathogenic in this disease model. These data indicate an alternative mode for T(H)17 differentiation. Consistent with genetic data linking IL23R with autoimmunity, our findings re-emphasize the importance of IL-23 and therefore may have therapeutic implications. |
