The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

Summary Group 2 innate lymphoid cells ( ILC 2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC 2s are tightly controlled by complex regulatory systems in the local microenvironment, the disruption of which may cause various health problems. This review summarizes up‐to‐date knowledge regarding positive and negative regulators for ILC 2s based on their function and signaling pathways, including activating cytokines ( IL ‐33, IL ‐25; MAPK , NF ‐κB pathways), co‐stimulatory cytokines ( IL ‐2, IL ‐7, IL ‐9, TSLP ; STAT 5, IL ‐4; STAT 6, TNF superfamily; MAPK , NF ‐κB pathways), suppressive cytokines (type1 IFN s, IFN ‐γ, IL ‐27; STAT 1, IL ‐10, TGF ‐β), transdifferentiation cytokines ( IL ‐12; STAT 4, IL ‐1β, IL ‐18), lipid mediators ( LTC 4, LTD 4, LTE 4, PGD 2; Ca 2+ ‐ NFAT pathways, PGE 2, PGI 2; AC / cAMP / PKA pathways, LXA 4, LTB 4), neuropeptides ( NMU ; Ca 2+ ‐ NFAT , MAPK pathways, VIP , CGRP , catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell‐to‐cell interactions ( ICOSL ‐ ICOS ; STAT 5, B7‐H6‐ NK p30, E‐cadherin‐ KLRG 1). This comprehensive review affords a better understanding of the regulatory network system for ILC 2s, providing impetus to develop new treatment strategies for ILC 2‐related health problems.