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. 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. 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 T_H 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. 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.