TY - JOUR
T1 - Group 2 Innate Lymphoid Cells in Airway Diseases
AU - Kato, Atsushi
N1 - Funding Information:
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.
Funding Information:
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.
Publisher Copyright:
© 2019 American College of Chest Physicians
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - ILC2
KW - allergic rhinitis
KW - asthma
KW - chronic rhinosinusitis with nasal polyps
KW - type 2 inflammation
UR - http://www.scopus.com/inward/record.url?scp=85067573423&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067573423&partnerID=8YFLogxK
U2 - 10.1016/j.chest.2019.04.101
DO - 10.1016/j.chest.2019.04.101
M3 - Review article
C2 - 31082387
AN - SCOPUS:85067573423
VL - 156
SP - 141
EP - 149
JO - Diseases of the chest
JF - Diseases of the chest
SN - 0012-3692
IS - 1
ER -