A new mechanism regulating the initiation of allergic airway inflammation

Attila Kiss; Martin Montes; Sarat Susarla; Elin A Jaensson; Scott M Drouin; Rick A Wetsel; Zhengbin Yao; Rachel Martin; Nabeel Hamzeh; Rebecca Adelagun; Sheila Amar; Farrah Kheradmand; David B Corry

doi:10.1016/j.jaci.2007.04.025

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A new mechanism regulating the initiation of allergic airway inflammation

Journal article

Open access

Peer reviewed

A new mechanism regulating the initiation of allergic airway inflammation

Attila Kiss, Martin Montes, Sarat Susarla, Elin A Jaensson, Scott M Drouin, Rick A Wetsel, Zhengbin Yao, Rachel Martin, Nabeel Hamzeh, Rebecca Adelagun, …

Journal of allergy and clinical immunology, Vol.120(2), pp.334-342

2007

DOI: 10.1016/j.jaci.2007.04.025

PMID: 17544098

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Abstract

The earliest immune events induced by allergens are poorly understood, yet are likely essential to understanding how allergic inflammation is established. We sought to describe the earliest signaling events activated by allergen and determine their significance to allergic inflammation. A fungal-associated allergenic proteinase (FAP) or ovalbumin was administered once intranasally to wild-type mice to determine their ability to induce allergy-associated genes and initiate allergic lung inflammation. Mice deficient in recombinase activating gene 1, C3a, the C3a anaphylatoxin receptor, and MyD88 were challenged similarly to understand the requirement of these molecules and T and B cells for allergic inflammation. Adoptive T-cell transfer experiments were further performed to determine whether signal transducer and activator of transcription 6 (STAT6) was required for cell recruitment and allergic inflammation. FAP, but not ovalbumin, induced eosinophilic airway inflammation and lung IL-4 production in the absence of adaptive immune cells after the transcriptional induction of allergy-specific airway chemokines. Allergen-mediated chemokine secretion and innate allergic lung inflammation occurred in the absence of STAT6, recombinase activating gene 1, C3a, C3a anaphylatoxin receptor, Toll-like receptor 4, and MyD88 but required intact proteinase activity. Furthermore, FAP induced recruitment of T H2 cells and eosinophils to lungs independently of STAT6, which was previously thought to be required for T H2 cell homing. FAP induces allergic lung inflammation through a previously unrecognized innate immune signaling mechanism. These findings reveal a new paradigm for understanding how allergic inflammation begins and suggest novel possibilities for the prevention and treatment of allergic diseases, such as asthma.

lung

T H1/T H2 cells

allergy

chemokines

inflammation

Details

Title: Subtitle: A new mechanism regulating the initiation of allergic airway inflammation
Creators: Attila Kiss - From the Departments of Medicine
Martin Montes - From the Departments of Medicine
Sarat Susarla - Pediatrics
Elin A Jaensson - Immunology, Baylor College of Medicine
Scott M Drouin - Institute of Molecular Medicine, University of Texas Health Science Center
Rick A Wetsel - Institute of Molecular Medicine, University of Texas Health Science Center
Zhengbin Yao - Tanox, Inc
Rachel Martin - Tanox, Inc
Nabeel Hamzeh - From the Departments of Medicine
Rebecca Adelagun - From the Departments of Medicine
Sheila Amar - From the Departments of Medicine
Farrah Kheradmand - From the Departments of Medicine
David B Corry - From the Departments of Medicine
Resource Type: Journal article
Publication Details: Journal of allergy and clinical immunology, Vol.120(2), pp.334-342
DOI: 10.1016/j.jaci.2007.04.025
PMID: 17544098
NLM abbreviation: J Allergy Clin Immunol
ISSN: 0091-6749
eISSN: 1097-6825
Publisher: Mosby, Inc
Language: English
Date published: 2007
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984094517202771

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