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Am J Respir Crit Care Med. 2011 May 1;183(9):1153-63. doi: 10.1164/rccm.201008-1383OC. Epub 2011 Feb 4.

Dual Role of IL-22 in allergic airway inflammation and its cross-talk with IL-17A.

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1
Université de Orléans and CNRS-UMR6218, Molecular Immunology and Embryology, 3B Rue de la Férollerie, 45071 Orléans Cedex 2, France.

Abstract

RATIONALE:

IL-22 has both proinflammatory and antiinflammatory properties. Its role in allergic lung inflammation has not been explored.

OBJECTIVES:

To investigate the expression and roles of IL-22 in the onset and resolution of experimental allergic asthma and its cross-talk with IL-17A.

METHODS:

IL-22 expression was assessed in patient samples and in the lung of mice immunized and challenged with ovalbumin. IL-22 functions in allergic airway inflammation were evaluated using mice deficient in IL-22 or anti-IL-22 neutralizing antibodies. Moreover, the effects of recombinant IL-22 and IL-17A neutralizing antibodies were investigated.

MEASUREMENTS AND MAIN RESULTS:

Increased pulmonary IL-22 expression is found in the serum of patients with asthma and mice immunized and challenged with ovalbumin. Allergic lung inflammation is IL-22 dependent because eosinophil recruitment, Th2 cytokine including IL-13 and IL-33, chemokine production, airway hyperreactivity, and mucus production are drastically reduced in mice deficient in IL-22 or by IL-22 antibody neutralization during immunization of wild-type mice. By contrast, IL-22 neutralization during antigen challenge enhanced allergic lung inflammation with increased Th2 cytokines. Consistent with this, recombinant IL-22 given with allergen challenge protects mice from lung inflammation. Finally, IL-22 may regulate the expression and proinflammatory properties of IL-17A in allergic lung inflammation.

CONCLUSIONS:

IL-22 is required for the onset of allergic asthma, but functions as a negative regulator of established allergic inflammation. Our study reveals that IL-22 contributes to the proinflammatory properties of IL-17A in experimental allergic asthma.

PMID:
21297073
DOI:
10.1164/rccm.201008-1383OC
[Indexed for MEDLINE]
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