Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid

Hideaki Morita, Terufumi Kubo, Beate Rückert, Avinash Ravindran, Michael B. Soyka, Arturo Ottavio Rinaldi, Kazunari Sugita, Marcin Wawrzyniak, Paulina Wawrzyniak, Kenichiro Motomura, Masato Tamari, Keisuke Orimo, Naoko Okada, Ken Arae, Kyoko Saito, Can Altunbulakli, Francesc Castro-Giner, Ge Tan, Avidan Neumann, Katsuko SudoLiam O'Mahony, Kenya Honda, Susumu Nakae, Hirohisa Saito, Jenny Mjösberg, Gunnar Nilsson, Kenji Matsumoto, Mübeccel Akdis, Cezmi A. Akdis

研究成果: Article査読

63 被引用数 (Scopus)

抄録

Background: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus clarification of the mechanisms that underlie regulation of ILC2 activation has received significant attention. Although innate lymphoid cells are divided into 3 major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T cells have not been well characterized. Objective: We sought to determine the factors that induce regulatory innate lymphoid cells (ILCregs). Methods: IL-10+ ILCregs induced from ILC2s by using retinoic acid (RA) were analyzed with RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissue from healthy subjects and patients with chronic rhinosinusitis with nasal polyps and lung tissue from house dust mite– or saline-treated mice. Results: RA induced IL-10 secretion by human ILC2s but not type 2 cytokines. IL-10+ ILCregs, which were converted from ILC2s by means of RA stimulation, expressed a regulatory T cell–like signature with expression of IL-10, cytotoxic T lymphocyte–associated protein 4, and CD25, with downregulated effector type 2–related markers, such as chemoattractant receptor–homologous molecule on TH2 cells and ST2, and suppressed activation of CD4+ T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy subjects or lung tissue from saline-treated mice, but numbers were increased in nasal tissue from patients with chronic rhinosinusitis with nasal polyps and in lung tissue from house dust mite–treated mice. Enzymes for RA synthesis were upregulated in airway epithelial cells during type 2 inflammation in vivo and by IL-13 in vitro. Conclusion: We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs.

本文言語English
ページ(範囲)2190-2201.e9
ジャーナルJournal of Allergy and Clinical Immunology
143
6
DOI
出版ステータスPublished - 2019 6

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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