T Helper Cell Differentiation, Heterogeneity, and Plasticity

Naïve CD4 T cells, on activation, differentiate into distinct T helper (Th) subsets that produce lineage-specific cytokines. By producing unique sets of cytokines, effector Th subsets play critical roles in orchestrating immune responses to a variety of infections and are involved in the pathogenesis of many inflammatory diseases including autoimmunity, allergy, and asthma. The differentiation of Th cells relies on the strength of T-cell receptor (TCR) signaling and signals triggered by polarizing cytokines that activate and/or up-regulate particular transcription factors. Several lineage-specific master transcription factors dictate Th cell fates and functions. Although these master regulators cross-regulate each other, their expression can be dynamic. Sometimes, they are even coexpressed, resulting in massive Th-cell heterogeneity and plasticity. Similar regulation mediated by these master regulators is also found in innate lymphoid cells (ILCs) that are innate counterparts of Th cells.