Molecular Mechanisms of T Helper Cell Differentiation and Functional Specialization

Abstract

Th cells, which orchestrate immune responses to various pathogens, differentiate from naïve CD4 T cells into several subsets that stimulate and regulate immune responses against various types of pathogens, as well as a variety of immune-related diseases. Decades of research have revealed that the fate decision processes are controlled by cytokines, cytokine receptor signaling, and master transcription factors that drive the differentiation programs. Since the Th1 and Th2 paradigm was proposed, many subsets have been added to the list. In this review, I will summarize these events, including the fate decision processes, subset functions, transcriptional regulation, metabolic regulation, and plasticity and heterogeneity. I will also introduce current topics of interest.

Keywords: Adaptive immune response; Cell differentiation; Cytokines; Helper T cell; T-lymphocyte subset; Transcription factors.

Figure 1. Schematic diagram of Th cell differentiation. Th cell differentiation pathway is determined by inducer cytokines that are present during T cell activation. The cytokine signaling activates STAT or SMAD, which in turn induces master transcription factors. Master transcription factors drive the subset-specific differentiation programs. Th cell proliferation and differentiation are also influenced by nutrient or metabolites.