Severe asthma in humans and mouse model suggests a CXCL10 signature underlies corticosteroid-resistant Th1 bias

Abstract

and as such, we focused on CXCL10, given its role in recruiting Th1 cells to reinforce type 1 inflammation to combat and eliminate viral and bacterial pathogens, a function that when uncontrolled can lead to significant pathology (13). The expression of CXCL10 can be induced not only by IFN-, but also by additional stimuli, including LPS, which can lead to differential levels of CXCL10 production and response to therapies In addition to its expression on Th1 cells, the CXCR3 receptorwhich mediates chemoattraction by CXCL10 and its family members -is also present on mast cells (17), neutrophils (18), and eosinophils (19). Elevated CXCL10 levels have been detected in multiple compartments, including blood and bronchoalveolar lavage (BAL) in mild and atopic asthma CXCL10 can be secreted by multiple cell types, including airway epithelial cells, smooth muscle cells, monocytes, and macrophages (11). However, several studies have implicated monocytes/macrophages as possible drivers of CXCL10 expression in asthma