Group 2 innate lymphoid cells in the regulation of immune responses

Type 2 cytokine-driven immune responses are important against parasite infections but also underlie the development of inflammatory allergic diseases. Type 2 CD4(+) T (Th2) cells have long been believed to act as central regulators of allergic conditions via the production of the signature cytokines IL-4, IL-5, and IL-13. However, the more recent identification of group 2 innate lymphoid cells ILC (ILC2) cells, which also produce the same cytokines, necessitates a reevaluation of the relative roles these two populations play during type 2 inflammation. ILC2 cells preferentially localize to the interface between the host and the environment (lung, intestine, skin) and respond to epithelium-derived cytokines associated with barrier disruption, such as IL-25, IL-33, and thymic stromal lymphopoietin. ILC2 cells are a major source of IL-5 and IL-13 in vivo but may also produce IL-4 and IL-9 under more defined conditions. ILC2 cells regulate local inflammatory responses to environmental challenges, and this in turn enables them to influence downstream adaptive immune responses. Here, we discuss our current understanding of ILC2 cell phenotype, development and function, and detail the expanding array of cell surface receptor and signaling pathways that enable ILC2 cells to perform a variety of biological functions in vivo. We give special attention to the most recently described and poorly understood member of the ILC2 cell family, the dermal ILC2 cells, and discuss their role in regulating skin inflammation.