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CCR 10 + ILC 2s with ILC 1‐like properties exhibit a protective function in severe allergic asthma
Author(s) -
Beuraud Chloé,
Lombardi Vincent,
Luce Sonia,
Horiot Stéphane,
Naline Emmanuel,
Neukirch Catherine,
Airouche Sabi,
Perchet Thibaut,
Golub Rachel,
Devillier Philippe,
CholletMartin Sylvie,
BaronBodo Véronique,
y Emmanuel,
Aubier Michel,
Mascarell Laurent,
Moingeon Philippe
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13679
Subject(s) - immunology , asthma , flow cytometry , medicine , allergic inflammation , inflammation , allergen , allergy
Background We previously showed that patients with severe allergic asthma have high numbers of circulating ILC 2s expressing CCR 10. Method Herein, CCR 10 + ILC 2s were further analyzed in the blood of healthy individuals or patients with allergic and non−allergic asthma. Characteristics of human CCR 10 + and CCR 10 − ILC 2s were assessed by flow cytometry as well as single‐cell multiplex RT ‐ qPCR . The role of CCR 10 + ILC 2s in asthma pathophysiology was studied in allergen‐treated mice. Results When compared to healthy controls, CCR 10 + ILC 2s are enriched in the blood of both allergic and non‐allergic severe asthmatic patients, and these cells are recruited to the lungs. Plasma concentrations of the CCR 10 ligand CCL 27 are significantly increased in severe asthmatics when compared to non‐asthmatic patients. CCR 10 + ILC 2s secrete little T H 2 cytokines, but exhibit ILC 1‐like properties, including a capacity to produce IFN ‐γ. Also, single‐cell analysis reveals that the CCR 10 + ILC 2 subset is enriched in cells expressing amphiregulin. CCR 10 + ILC 2 depletion, as well as blocking of IFN ‐γ activity, exacerbates airway hyperreactivity in allergen‐challenged mice, providing evidence for a protective role of these cells in allergic inflammation. Conclusions Frequencies of circulating CCR 10 + ILC 2s and CCL 27 plasma concentrations represent candidate markers of asthma severity. The characterization of CCR 10 + ILC 2s in human samples and in mouse asthma models suggests that these cells downregulate allergic inflammation through IFN ‐γ production.