TGFβ is the quintessential cytokine of T cell homeostasis. TGFβ 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, TGFβ promotes Th17 cell differentiation. The 
mechanism by which TGFβ signals synergize with IL-6 to generate inflammatory 
versus immunosuppressive T cell subsets is unclear. TGFβ 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 TGFβ-signaling pathways that tailor TGFβ 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 TGFβ 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 
TGFβ signaling in CD4(+) T effector cell differentiation.