The Role of Protein Modifications of T-Bet in Cytokine Production and Differentiation of T Helper Cells

Figure 2

Multiple T-bet functions playing a role in Th cell differentiation. Induction of T-bet expression through activation of STAT1 and STAT4 directly stimulates the transcription of T-box-binding element-containing genes, such as IFNG, IL12RB2, and CXCR3, thereby enhancing Th1 cell development. T-Bet undergoes serine phosphorylation at S508 and then downregulates IL-2 production in Th1 cells by recruiting NF-κB p65 from the IL2 promoter. Protein levels of T-bet in Th1 cells can be controlled by the ubiquitin-mediated proteasomal degradation pathway. Moreover, T-bet protein undergoes additional posttranslational modifications, for example, phosphorylation at T302 and Y525, which facilitates its suppression of the Th2 cytokine production that is induced by activation of NFAT and GATA-3.