Eosinopenia and ILC2 Immune Dysfunction in COPD Exacerbation is Associated to the Upregulation of ILC3/IL-22 Axis

<bold>Background:</bold> Eosinopenia is associated to bacterial COPD exacerbation (B-ECOPD). Immunity governed by group 2 innate lymphoid cells (ILC2s) is partially responsible for the accumulation of eosinophils in COPD. IL-22 has a suppressing effect on eosinophilic inflammation, and ILC3s are one of the main sources of it. The involvement of ILC2s immunity and ILC3/IL-22 axis in the development of eosinopenia in B-ECOPD has not been discovered yet. <bold>Methods:</bold> First, we observed the presence of blood eosinopenia in ECOPD patients in cross-sectional cohort. The blood samples were evaluate the relationship between eosinopenia, ILC2 immune responsiveness, and the level of ILC3/IL-22 axis. Then, we confirmed the observations made in human cohort by establishing ECOPD mice models. The expression of IL-22 and accumulation of IL-22 producing ILC3s in mice lung tissues were detected through multiple techniques. Last, recombinant mouse IL-22, was endotracheally administrated in ECOPD mice models, and the effect of IL-22 in mice lung tissues was profiled by using the transcriptome sequencing and proteomics mass spectra. Findings The patient cohort showed a significant blood eosinopenia in individuals with B-ECOPD. A downregulated ILC2 immunity and an upregulated ILC3/IL-22 axis in blood were observed to be closely related to eosinopenia in B-ECOPD patients. The eosinopenia, ILC2 immune dysfunction, and increased IL-22 production were confirmed in lung tissues of ECOPD mice, along with an increase of IL-22 producing ILC3s. IL-22 aggravated the inflammation, eosinopenia, ILC2 immune suppression and induced a remarkable inhibition in type 2 immunity in lung tissues of ECOPD mice.