Type 2 Innate Lymphoid Cells in Liver and Gut: From Current Knowledge to Future Perspectives

Innate lymphoid cells (ILCs) represent a heterogeneous population of recently discovered immune cells that mirror the functions of adaptive T lymphocytes. However, ILCs are devoid of specific antigen receptors and cellular activation depends on environmental cytokines, rendering them as early regulators of immune responses. Type 2 innate lymphoid cells (ILC2s) respond to alarmins, such as interleukin-25 and -33 and shape Th2-associated immunity by expressing IL-5 and IL-13 in a GATA3-dependent manner. In addition, ILC2s express the epidermal growth factor-like molecule Amphiregulin thereby promoting regeneration of injured tissue during inflammation. The gut and liver confer nutrient metabolism and bidirectional exchange of products, known as the gut-liver axis. Accordingly, both organs are continuously exposed to a large variety of harmless antigens. This requires avoidance of immunity, which is established by a tolerogenic environment in the gut and liver. However, dysregulations within the one organ are assumed to influence vitality of the other and frequently promote chronic inflammatory settings with poor prognosis. Intensive research within the last years has revealed that ILC2s are involved in acute and chronic inflammatory settings of gut and liver. Here, we highlight the roles of ILC2s in intestinal and hepatic inflammation and discuss a regulatory potential.