Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors

CD4(+) T cells, also known as T-helper (Th) cells, play an important role in orchestrating adaptive immune responses to various infectious agents. They are also involved in the induction of autoimmune and allergic diseases. Upon T-cell receptor (TCR)-mediated cell activation, naive CD4(+) T cells can differentiate into at least four major lineages, Th1, Th2, Th17, and iTreg cells, that participate in different types of immune responses. Networks of cytokines and transcription factors are critical for determining CD4(+) T-cell fates and effector cytokine production. Here, we review collaboration and cross-regulation between various essential cytokines in the activation/induction of key transcription factors during the process of Th cell differentiation towards these distinct lineages. We also discuss the interactions of key transcription factors at both genetic and protein levels and the function of the resulting network(s) in regulating the expression of effector cytokines.