Homeostatic and early-recruited CD101⁻ eosinophils suppress endotoxin-induced acute lung injury

Abstract

RationaleAcute lung injury (ALI) is a fatal but undertreated condition with severe neutrophilic inflammation, while little is known about the functions of eosinophils in pathogenesis of ALI.ObjectivesTo investigate the roles and molecular mechanisms of eosinophils in ALI.MethodsPulmonary eosinophils were identified by flow cytometry. Mice with abundant or deficient eosinophils were used. Cellularity of eosinophils and neutrophils in BALF, inflammatory assessment, and survival rate were detected. Human samples were also used for validating experimental results.ResultsBlood eosinophils were increased in survived individuals of patients with acute respiratory distress syndrome independent of the corticosteroid usage. There existed homeostatic eosinophils in lung parenchyma in mice, and these homeostatic eosinophils in originating from the bone marrow were predominantly CD101−. More CD101− eosinophils could be recruited earlier than lipopolysaccharide (LPS)-initiated neutrophilic inflammation. Loss of eosinophils augmented LPS-induced pulmonary injury. Homeostatic CD101− eosinophils ameliorated, while allergic CD101+ eosinophils exacerbated, the neutrophilic inflammation induced by LPS. Likewise, CD101 expression in eosinophils from ARDS patients did not differ from the healthy subjects. Mechanistically, CD101− eosinophils exhibited higher levels of Alox15 and Protectin D1. Administration of Protectin D1 isomer attenuated the neutrophilic inflammation.ConclusionsCollectively, our findings identify an uncovered function of native CD101− eosinophils in suppressing neutrophilic lung inflammation and suggest a potential therapeutic target for ALI.

Blood eosinophils and mortality in patients with acute respiratory distress syndrome: A propensity score matching analysis

“…[11] Recently, a retrospective analysis of 112 patients with ARDS found that ARDS surviving patients have higher blood EOS counts than non-survivors and that EOSs may play a protective role in ARDS independent of corticosteroid use. [12] The prognosis of ARDS patients is closely related to factors such as tidal volume. [13,14] The relationship between blood EOSs and mortality in patients with ARDS needs to be further evaluated with a large sample size after full consideration of confounders.…”

Severity-associated markers and assessment model for predicting the severity of COVID-19: a retrospective study in Hangzhou, China

“…Among the eight markers in our model, LDH, CRP, ALB, and lymphocyte count were well-recognized predictors for COVID-19 severity [13]. For eosinophil count, Zhu et al [14] demonstrated that decreased eosinophils could induce acute lung injury in the mouse model.…”

Decreased eosinophil counts and elevated lactate dehydrogenase predict severe COVID-19 patients with underlying chronic airway diseases

“…Circulating eosinophil counts were reported to gradually increase patients [28]. A recent study has highlighted the signi cant role of CD101 − eosinophils in suppressing acute lung injury and respiratory failure [29]. Therefore, eosinophil could have helped patients with chronic airway in ammation escape from SARS-CoV-2 infections and has been identi ed as a probable potential indicator for prognosis in COVID-19.…”