1 research outputs found
Th2 and Th17 inflammatory pathways are reciprocally regulated in asthma
Increasing evidence suggests that asthma is a heterogeneous disorder regulated
by distinct molecular mechanisms. Here, in a cross-sectional study of asthmatics
of varying severity (n=51), endobronchial tissue gene expression analysis
revealed three major patient clusters: Th2-high, Th17-high, and Th2/Th17-low.
Th2-high and Th17-high patterns were mutually exclusive in individual patient
samples, and their gene signatures were inversely correlated and differentially
regulated by IL-13 and IL-17A. To understand this dichotomous pattern of Th2
and Th17 signatures, we investigated the potential of type 2 cytokine
suppression in promoting Th17 responses in a preclinical model of allergen
induced asthma. Neutralization of IL-4 and/or IL-13 resulted in increased Th17
cells and neutrophilic inflammation in the lung. However, neutralization of IL-1
and IL-17 protected subjects from eosinophilia, mucus hyperplasia, airway
hyperreactivity and abolished the neutrophilic inflammation, suggesting that
combination therapies targeting both pathways may maximize therapeutic
efficacy across a patient population comprising both Th2 and Th17 endotypes