TH2 cell development and function

Key Points T helper 2 (T H 2) cells respond to a variety of environmental cues, either directly or indirectly through interaction with cells of the innate immune system. For instance, certain specialized dendritic cells (DCs) promote T H 2 cell induction, whereas other DC subsets are suppressive. Epithelial cell-derived cytokines, such as IL-25, IL-33 and thymic stromal lymphopoietin (TSLP), and IL-4-producing immune cells, such as innate lymphoid cells and basophils, can potentiate T H 2 cell responses. However, the relative importance of these innate cell stimuli for T H 2 cell development remains to be determined and is likely to be dependent on local environmental cues. T H 2 cell differentiation is fundamentally dependent on the mechanistic target of rapamycin-mediated metabolic transition from oxidative phosphorylation to aerobic glycolysis. T H cell subsets are somewhat heterogeneous in terms of their cytokine secretion and transcription factor profiles. Single-cell technologies promise to deliver new insight into how T H cells integrate diverse environmental cues to ensure their adaptability during homeostasis, protective immunity and tissue repair. Our evolving knowledge of T H 2 cell differentiation at the molecular and cellular levels has led to the development of novel therapies targeting specific transcription factors and T H 2 cell-associated cytokines. This Review describes our current understanding of the mechanisms regulating T helper 2 (T H 2) cell development and function. The authors discuss how our increasing comprehension of these pathways is leading to the development of novel therapies for T H 2 cell-mediated diseases, such as asthma and allergy. T helper 2 (T H 2) cells orchestrate protective type 2 immune responses, such as those that target helminths and facilitate tissue repair, but also contribute to chronic inflammatory diseases, such as asthma and allergy. Here, we review recent insights into how diverse molecular signals from cellular sources, including dendritic cells, innate lymphoid cells and the epithelium, are integrated by T cells to guide the transcriptional and epigenetic changes necessary for T H 2 cell differentiation. Our improved understanding of these pathways has opened new avenues for therapeutically targeting T H 2 cells in asthma and allergy. The advent of comprehensive single-cell transcriptomics along with improvements in single-cell proteomics and the generation of novel in vivo cell fate mapping techniqu