期刊
MUCOSAL IMMUNOLOGY
卷 9, 期 2, 页码 539-549出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2015.83
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资金
- National Research Agency via the Investment Into The Future program [ANR-10-IBHU-005]
- Nantes Metropole
- Pays de la Loire Region
- CHU Nantes (Appel d'offre interne) [RC14_0042]
- CHU de Nantes through Annee Supplementaire d'Internat
- Region Pays de la Loire through the IMBIO-DC network
- French-tunisian UTIQUE grant from the Hubert Curien program
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.
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