Regulation of T helper cell differentiation by E3 ubiquitin ligases and deubiquitinating enzymes

•CD4 T cell differentiation is regulated by TCR, costimulatory and cytokine signals•E3s-mediated ubiquitination is critically involved in CD4 T cell differentiation•DUBs-mediated deubiquitination is essential for CD4 T cell differentiation

CD4 T cells are essential components of adaptive immunity and play a critical role in anti-pathogenic or anti-tumor responses as well as autoimmune and allergic diseases. Naive CD4 T cells differentiate into distinct subsets of T helper (Th) cells by various signals including TCR, costimulatory and cytokine signals. Accumulating evidence suggests that these signaling pathways are critically regulated by ubiquitination and deubiquitination, two reversible posttranslational modifications mediated by E3 ubiquitin ligases and deubiquitinating enzymes (DUBs), respectively. In this review, we briefly introduce the signaling pathways that control the differentiation of Th cells and then focused on the roles of E3s- and DUBs-mediated ubiquitin modification or demodification in regulating Th cell differentiation.