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CCR10 + ILC2s with ILC1-like properties exhibit a protective function in severe allergic asthma

Abstract : We previously showed that patients with severe allergic asthma have high numbers of circulating ILC2s expressing CCR10. METHOD: Herein, CCR10+ ILC2s were further analyzed in the blood of healthy individuals or patients with allergic and non-allergic asthma. Characteristics of human CCR10+ and CCR10- ILC2s were assessed by flow cytometry as well as single-cell multiplex RT-qPCR. The role of CCR10+ ILC2s in asthma pathophysiology was studied in allergen-treated mice. RESULTS: When compared to healthy controls, CCR10+ ILC2s 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 CCR10 ligand CCL27 are significantly increased in severe asthmatics when compared to non-asthmatic patients. CCR10+ ILC2s secrete little TH 2 cytokines, but exhibit ILC1-like properties, including a capacity to produce IFN-γ. Also, single-cell analysis reveals that the CCR10+ ILC2 subset is enriched in cells expressing amphiregulin. CCR10+ ILC2 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 CCR10+ ILC2s and CCL27 plasma concentrations represent candidate markers of asthma severity. The characterization of CCR10+ ILC2s in human samples and in mouse asthma models suggests that these cells downregulate allergic inflammation through IFN-γ production.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01969375
Contributor : Marie-Christine Vougny <>
Submitted on : Friday, January 4, 2019 - 9:31:45 AM
Last modification on : Wednesday, October 14, 2020 - 4:15:18 AM

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Chloé Beuraud, Vincent Lombardi, Sonia Luce, Stéphane Horiot, Emmanuel Naline, et al.. CCR10 + ILC2s with ILC1-like properties exhibit a protective function in severe allergic asthma. Allergy, Wiley, In press, ⟨10.1111/all.13679⟩. ⟨pasteur-01969375⟩

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