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

TitlePathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A.
Publication TypeJournal Article
Year of Publication2010
AuthorsSonnenberg GF, Nair MG, Kirn TJ, Zaph C, Fouser LA, Artis D
JournalJ Exp Med
Date Published2010 Jun 7
KeywordsAnimals, Antibodies, Monoclonal, Antibodies, Neutralizing, Apoptosis, Bleomycin, Epithelial Cells, Interleukin-17, Interleukins, Mice, Mice, Inbred C57BL, Pneumonia, T-Lymphocytes, Helper-Inducer

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.

Alternate JournalJ. Exp. Med.
PubMed ID20498020
PubMed Central IDPMC2882840
Grant ListAI083480 / AI / NIAID NIH HHS / United States
AI61570 / AI / NIAID NIH HHS / United States
AI74878 / AI / NIAID NIH HHS / United States
T32AI007532-08 / AI / NIAID NIH HHS / United States

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