IL-22BP is produced by eosinophils in human gut and blocks IL-22 protective actions during colitis

J. C. Martin, G. Bériou, M. Heslan, C. Bossard, A. Jarry, A. Abidi, P. Hulin, S. Ménoret, R. Thinard, I. Anegon, C. Jacqueline, B. Lardeux, F. Halary, J. C. Renauld, A. Bourreille, R. Josien

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel diseases (IBDs), are characterized by high levels of IL-22 production. Rodent studies revealed that this cytokine is protective during colitis but whether this is true in IBDs is unclear. We show here that levels of the soluble inhibitor of IL-22, interleukin 22-binding protein (IL-22BP), are significantly enhanced during IBDs owing to increased numbers of IL-22BP-producing eosinophils, that we unexpectedly identify as the most abundant source of IL-22BP protein in human gut. In addition, using IL-22BP-deficient rats, we confirm that endogenous IL-22BP is effective at blocking protective actions of IL-22 during acute colitis. In conclusion, our study provides new important insights regarding the biology of IL-22 and IL-22BP in the gut and indicates that protective actions of IL-22 are likely to be suboptimal in IBDs thus making IL-22BP a new relevant therapeutic target.

Original languageEnglish
Pages (from-to)539-549
Number of pages11
JournalMucosal Immunology
Volume9
Issue number2
DOIs
StatePublished - 1 Mar 2016
Externally publishedYes

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