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

Hiroki Kabata, Kazuyo Moro, Shigeo Koyasu

Research output: Contribution to journalReview article

46 Citations (Scopus)

Abstract

Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC2s 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 ILC2s 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; STAT5, IL-4; STAT6, TNF superfamily; MAPK, NF-κB pathways), suppressive cytokines (type1 IFNs, IFN-γ, IL-27; STAT1, IL-10, TGF-β), transdifferentiation cytokines (IL-12; STAT4, IL-1β, IL-18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca2+-NFAT pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca2+-NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell-to-cell interactions (ICOSL-ICOS; STAT5, B7-H6-NKp30, E-cadherin-KLRG1). This comprehensive review affords a better understanding of the regulatory network system for ILC2s, providing impetus to develop new treatment strategies for ILC2-related health problems.

Original languageEnglish
Pages (from-to)37-52
Number of pages16
JournalImmunological Reviews
Volume286
Issue number1
DOIs
Publication statusPublished - 2018 Nov

Keywords

  • IL-25
  • IL-33
  • ILC2
  • TSLP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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