Complement-mediated Regulation of the IL-17A Axis is a Central Genetic Determinant of the Severity of Experimental Allergic Asthma

Overview

Journal Nat Immunol

Date 2010 Aug 31

PMID 20802484

Citations 176

Authors

Stephane Lajoie

Ian P Lewkowich

Yusuke Suzuki

Jennifer R Clark

Alyssa A Sproles

Krista Dienger

Alison L Budelsky

Marsha Wills-Karp

Affiliations

Soon will be listed here.

Abstract

Severe asthma is associated with the production of interleukin 17A (IL-17A). The exact role of IL-17A in severe asthma and the factors that drive its production are unknown. Here we demonstrate that IL-17A mediated severe airway hyperresponsiveness (AHR) in susceptible strains of mice by enhancing IL-13-driven responses. Mechanistically, we demonstrate that IL-17A and AHR were regulated by allergen-driven production of anaphylatoxins, as mouse strains deficient in complement factor 5 (C5) or the complement receptor C5aR mounted robust IL-17A responses, whereas mice deficient in C3aR had fewer IL-17-producing helper T cells (T(H)17 cells) and less AHR after allergen challenge. The opposing effects of C3a and C5a were mediated through their reciprocal regulation of IL-23 production. These data demonstrate a critical role for complement-mediated regulation of the IL-23-T(H)17 axis in severe asthma.

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