Description

Effective immune responses depend upon appropriate T cell differentiation in accord with the nature of an infectious agent, and the contingency of differentiation depends minimally on T cell antigen receptor, co-receptor, and cytokine signals. In this reverse genetic study we show that the Map Kinase, Erk2, is nonessential for T cell proliferation in the presence of optimum co-stimulation. Instead, it has opposite polar effects on T-bet and Gata3 expression and hence on Th1 and Th2 differentiation. Alternatively, in the presence of TGFbeta, the Erk pathway suppresses a large program of gene expression effectively limiting the differentiation of Foxp3+ T reg cells. In the latter case, the mechanisms involved include suppression of Gata3 and Foxp3, induction of Tbx21, phosphorylation of Smad2,3, and possibly suppression of Socs2, a positive inducer of Stat5 signaling. Consequently, loss of Erk2 severely impeded Th1 differentiation while enhancing the development of Foxp3+ induced T regulatory cells. Selected profiles of gene expression under multiple conditions of T cell activation illustrate the opposing consequences of Erk pathway signaling.

Publication Title

Polar opposites: Erk direction of CD4 T cell subsets.

Sample Metadata Fields

Specimen part, Time