In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 7, No. 301 ( 2015-08-19)
Abstract:
Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In a cross-sectional study of asthmatics of varying severity ( n = 51), endobronchial tissue gene expression analysis revealed three major patient clusters: T H 2-high, T H 17-high, and T H 2/17-low. T H 2-high and T H 17-high patterns were mutually exclusive in individual patient samples, and their gene signatures were inversely correlated and differentially regulated by interleukin-13 (IL-13) and IL-17A. To understand this dichotomous pattern of T helper 2 (T H 2) and T H 17 signatures, we investigated the potential of type 2 cytokine suppression in promoting T H 17 responses in a preclinical model of allergen-induced asthma. Neutralization of IL-4 and/or IL-13 resulted in increased T H 17 cells and neutrophilic inflammation in the lung. However, neutralization of IL-13 and IL-17 protected mice from eosinophilia, mucus hyperplasia, and airway hyperreactivity and abolished the neutrophilic inflammation, suggesting that combination therapies targeting both pathways may maximize therapeutic efficacy across a patient population comprising both T H 2 and T H 17 endotypes.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.aab3142
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2015
