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

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.

• Authors: Anne-Gaelle Besnard, Robert Sabat, Laure Dumoutier, Jean-Christophe Renauld, Monique Willart, Bart Lambrecht, Mauro M Teixeira, Sabine Charron, Lizette Fick, François Erard, Katarzyna Warszawska, Kerstin Wolk, Valerie Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 183 Issue 9 Pg. 1153-63 (May 01 2011) ISSN: 1535-4970 [Electronic] United States
• PMID: 21297073 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Cytokines
• Interleukin-17
• Interleukins
• interleukin-22

Topics

• Animals
• Asthma (blood, immunology)
• Chemokines (immunology)
• Cytokines (immunology)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Eosinophils (immunology)
• Flow Cytometry
• Humans
• Interleukin-17 (immunology)
• Interleukins (blood, immunology)
• Mice
• Mice, Knockout
• Th2 Cells (immunology)