Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A

Journal of Experimental Medicine - Tập 207 Số 6 - Trang 1293-1305 - 2010
Gregory F. Sonnenberg1, Meera G. Nair2, Thomas J. Kirn2, Colby Zaph2, Lynette A. Fouser3, David Artis2
1Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA
2Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104 1
3Inflammation and Immunology–Pfizer BioTherapeutics Research and Development, Cambridge, MA 02140 2

Tóm tắt

IL-22 has both proinflammatory and tissue-protective properties depending on the context in which it is expressed. However, the factors that influence the functional outcomes of IL-22 expression remain poorly defined. We demonstrate that after administration of a high dose of bleomycin that induces acute tissue damage and airway inflammation and is lethal to wild-type (WT) mice, Th17 cell–derived IL-22 and IL-17A are expressed in the lung. Bleomycin-induced disease was ameliorated in Il22−/− mice or after anti–IL-22 monoclonal antibody (mAb) treatment of WT mice, indicating a proinflammatory/pathological role for IL-22 in airway inflammation. However, despite increased bleomycin-induced IL-22 production, Il17a−/− mice were protected from airway inflammation, suggesting that IL-17A may regulate the expression and/or proinflammatory properties of IL-22. Consistent with this, IL-17A inhibited IL-22 production by Th17 cells, and exogenous administration of IL-22 could only promote airway inflammation in vivo by acting in synergy with IL-17A. Anti–IL-22 mAb was delivered to Il17a−/− mice and was found to exacerbate bleomycin-induced airway inflammation, indicating that IL-22 is tissue protective in the absence of IL-17A. Finally, in an in vitro culture system, IL-22 administration protected airway epithelial cells from bleomycin-induced apoptosis, and this protection was reversed after coadministration of IL-17A. These data identify that IL-17A can regulate the expression, proinflammatory properties, and tissue-protective functions of IL-22, and indicate that the presence or absence of IL-17A governs the proinflammatory versus tissue-protective properties of IL-22 in a model of airway damage and inflammation.

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Journal of Experimental Medicine

Tập 207 Số 6

1293-1305

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