Increased METEORIN-LIKE (ML) expression promotes lung inflammation in asthma

Abstract

Background: Meteorin-like (ML) increases the eosinophil infiltration into mouse subcutaneous adipose tissue. We hypothesized that ML is involved in the pathogenesis of eosinophilic asthma (EA).

Methods: We examined ML expression in asthmatic patients from a discovery and validation cohorts and examine the effect of ML on eosinophil recruitment into the airways in a murine model of EA and in human airway epithelial cell（HBE） function in vitro.

Results: In a discovery cohort of 105 asthmatics and 20 control subjects, serum ML levels (asthmatics: 613.31±45.16 VS control:89.07±20.78pg/ml, p<0.0001) correlated with asthma severity (r=-0.5067 p<0.0001), poor asthma control (r=-0.4797 p<0.0001) and decreased lung function (r=-0.3732 p=0.0002). We validated the increase in serum ML levels in the COREA cohort (748 asthmatics, 161 healthy controls; 1156.03±23.19 VS 536.20±38.23pg/ml, p< 0.0001). ML levels were consistent over a 1-year follow-up period. ML expression was elevated in the serum (244.80±45.11VS 93.14±20.86 pg/ml, p=0.0021) and BAL (738.70±78.59 VS 299.00±56.36 pg/ml, p=0.0003) of a mouse model of asthma and mainly located within lung macrophages. ML mRNA and protein expression and release from mouse macrophages was up-regulated by IL-4/IL-13 in a JAK/STAT-dependent manner. Recombinant ML drove eosinophilic airway inflammation in vivo in mice and enhanced the expression of the eotaxin receptor CCR3 in mouse and HBEs in vitro. Sputum ML mRNA significantly correlated with sputum eosinophil and with CCR3 mRNA expression in HBEs in the U-BIOPRED consortia.

Conclusions: Our study is the first to demonstrate enhanced ML expression in asthma and that ML is involved in the pathogenesis of EA.