| First Author | Malhotra N | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 38 | Pages | 29044-8 |
| PubMed ID | 20656683 | Mgi Jnum | J:166386 |
| Mgi Id | MGI:4844220 | Doi | 10.1074/jbc.C110.156745 |
| Citation | Malhotra N, et al. (2010) SMAD2 is essential for TGF beta-mediated Th17 cell generation. J Biol Chem 285(38):29044-8 |
| abstractText | TGFbeta is the quintessential cytokine of T cell homeostasis. TGFbeta signaling is required for the efficient differentiation and maintenance of CD4(+)FOXP3(+) T cells that inhibit immune responses. Conversely, in conjunction with the inflammatory cytokine IL-6, TGFbeta promotes Th17 cell differentiation. The mechanism by which TGFbeta signals synergize with IL-6 to generate inflammatory versus immunosuppressive T cell subsets is unclear. TGFbeta signaling activates receptor SMADs, SMAD2 and SMAD3, which associate with a variety of nuclear factors to regulate gene transcription. Defining relative contributions of distinct SMAD molecules for CD4 T cell differentiation is critical for mapping the versatile intracellular TGFbeta-signaling pathways that tailor TGFbeta activities to the state of host interaction with pathogens. We show here that SMAD2 is essential for Th17 cell differentiation and that it acts in part by modulating the expression of IL-6R on T cells. Although mice lacking SMAD2 specifically in T cells do not develop spontaneous lymphoproliferative autoimmunity, Smad2-deficient T cells are impaired in their response to TGFbeta in vitro and in vivo, and they are more pathogenic than controls when transferred into lymphopenic mice. These results demonstrate that SMAD2 is uniquely essential for TGFbeta signaling in CD4(+) T effector cell differentiation. |
