Group 2 Innate Lymphoid Cells in Airway Diseases

Atsushi Kato*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

148 Scopus citations

Abstract

Group 2 innate lymphoid cells (ILC2s) are increasingly recognized as a key controller of type 2 inflammation, and are well known to be highly elevated in human airway type 2 inflammatory diseases including allergic rhinitis, chronic rhinosinusitis with nasal polyps, and asthma. ILC2-mediated production of type 2 cytokines initiates and amplifies airway inflammation via activation of eosinophils, B cells, mast cells, macrophages, fibroblasts, and epithelial cells in these diseases. ILC2s require at least three major signals to fully activate and robustly produce type 2 cytokines. IL-1 family cytokines (IL-1β, IL-18, IL-33), IL-25, and TNF superfamilies (TNF, TL1A, GITR-L, RANK-L) activate the NF-κB and AP-1 pathways that initiate production of IL-5 and IL-13. Lipid mediators (LTC4, LTD4, PGD2) and neuropeptide NMU promote production of IL-4 through the NFAT pathway. IL-2 and IL-7 family cytokines (IL-2, IL-7, IL-9, TSLP) activate the STAT5 pathway that induces survival of ILC2s and enhances cytokine production. The activation of STAT5 is necessary to potently induce cytokine- and lipid mediator-mediated production of type 2 cytokines. Inhibitory pathways for ILC2s have also become clearer. Type I and II interferons and IL-27 inhibit ILC2 functions through the activation of STAT1. Suppression mediated via β2-adrenergic receptor agonists, PGE2, and PGI2 occurs through cAMP and PKA. Glucocorticoid, testosterone, IL-10, and TGF-β are also able to inhibit ILC2-mediated production of type 2 cytokines. Blockage of ILC2 activators, activation of inhibitory pathways of ILC2s, and suppression of ILC2-mediated pathways including type 2 cytokines (IL-5, IL-13, IL-4Ra) may become therapeutic strategies for airway type 2 inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)141-149
Number of pages9
JournalCHEST
Volume156
Issue number1
DOIs
StatePublished - Jul 2019

Funding

FUNDING/SUPPORT: This research was supported in part by NIH grants [R01 AI104733, R01 AI137174, R37 HL068546, and U19 AI106683] and by grants from Janssen Research and the Ernest S. Bazley Foundation.Financial/nonfinancial disclosures: The author has reported to CHEST the following: A. K. has received grants from the National Institutes of Health (R01 AI104733, R01 AI137174, R37 HL068546, and U19 AI106683), Janssen Research, and the Ernest S. Bazley Foundation and has received payment for a lecture from Janssen Research. Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript. Other contributions: The author acknowledges Ms Julie Poposki for proofreading of this review. FUNDING/SUPPORT: This research was supported in part by NIH grants [ R01 AI104733, R01 AI137174, R37 HL068546, and U19 AI106683] and by grants from Janssen Research and the Ernest S. Bazley Foundation. Financial/nonfinancial disclosures: The author has reported to CHEST the following: A. K. has received grants from the National Institutes of Health ( R01 AI104733 , R01 AI137174 , R37 HL068546 , and U19 AI106683 ), Janssen Research, and the Ernest S. Bazley Foundation and has received payment for a lecture from Janssen Research.

Keywords

  • ILC2
  • allergic rhinitis
  • asthma
  • chronic rhinosinusitis with nasal polyps
  • type 2 inflammation

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine

Fingerprint

Dive into the research topics of 'Group 2 Innate Lymphoid Cells in Airway Diseases'. Together they form a unique fingerprint.

Cite this