Critical role of caspase-8–mediated IL-1 signaling in promoting Th2 responses during asthma pathogenesis

Xiaopeng Qi; Prajwal Gurung; R. K. Subbarao Malireddi; Peer W. F Karmaus; Deepika Sharma; Peter Vogel; Hongbo Chi; Douglas R Green; Thirumala-Devi Kanneganti

doi:10.1038/mi.2016.25

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Critical role of caspase-8–mediated IL-1 signaling in promoting Th2 responses during asthma pathogenesis

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Critical role of caspase-8–mediated IL-1 signaling in promoting Th2 responses during asthma pathogenesis

Xiaopeng Qi, Prajwal Gurung, R. K. Subbarao Malireddi, Peer W. F Karmaus, Deepika Sharma, Peter Vogel, Hongbo Chi, Douglas R Green and Thirumala-Devi Kanneganti

Mucosal immunology, Vol.10(1), pp.128-138

03/01/2016

DOI: 10.1038/mi.2016.25

PMCID: PMC5035164

PMID: 27007676

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Abstract

Allergic asthma is a chronic inflammatory disorder of the airways that affects more than 300 million people worldwide. The pro-inflammatory cytokines IL-1α and IL-1β play essential roles in the pathogenesis of asthma. However, the mechanisms underlying the production of IL-1 cytokines in allergic asthma remain unclear. In this study, we used a mouse model of ovalbumin (OVA)–induced asthma to identify a crucial role for caspase-8 in the development of allergic airway inflammation. We further demonstrated that hematopoietic cells play dominant roles in caspase-8–mediated allergic airway inflammation. Caspase-8 was required for the production of IL-1 cytokines to promote Th2 immune response, which promotes the development of pulmonary eosinophilia and inflammation. Thus, our study identifies caspase-8 as a master regulator of IL-1 cytokines that contribute to the pathogenesis of asthma and implicates caspase-8 inhibition as a potential therapeutic strategy for asthmatic patients.

caspase-8

asthma

respiratory tract diseases

inflammasomes

airway

Article

Details

Title: Subtitle: Critical role of caspase-8–mediated IL-1 signaling in promoting Th2 responses during asthma pathogenesis
Creators: Xiaopeng Qi
Prajwal Gurung
R. K. Subbarao Malireddi
Peer W. F Karmaus
Deepika Sharma
Peter Vogel
Hongbo Chi
Douglas R Green
Thirumala-Devi Kanneganti
Resource Type: Journal article
Publication Details: Mucosal immunology, Vol.10(1), pp.128-138
DOI: 10.1038/mi.2016.25
PMID: 27007676
PMCID: PMC5035164
ISSN: 1933-0219
eISSN: 1935-3456
Grant note: 2R01AR056296-11 / National Institutes of Health (nih_________::NIH) 5R01AI101935-03 / National Institutes of Health (nih_________::NIH) 1R01CA163507-01A1 / National Institutes of Health (nih_________::NIH)
Language: English
Date published: 03/01/2016
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094669802771

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