A pathogenic role for T cell-derived IL-22BP in inflammatory bowel disease

作者：Pelczar Penelope; Witkowski Mario; Perez Laura Garcia; Kempski Jan; Hammel Anna G; Brockmann Leonie; Kleinschmidt Dorte; Wende Sandra; Haueis Cathleen; Bedke Tanja; Witkowski Marco; Krasemann Susanne; Steurer Stefan; Booth Carmen J; Busch Philipp; Koenig Alexandra; Rauch Ursula; Benten Daniel; Izbicki Jakob R; Roesch Thomas; Lohse Ansgar W; Strowig Till; Gagliani Nicola; Flavell Richard A^*; Huber Samuel^*

来源：Science, 2016, 354(6310): 358-362.

DOI：10.1126/science.aah5903

Intestinal inflammation can impair mucosal healing, thereby establishing a vicious cycle leading to chronic inflammatory bowel disease (IBD). However, the signaling networks driving chronic inflammation remain unclear. Here we report that CD4(+) T cells isolated from patients with IBD produce high levels of interleukin-22 binding protein (IL-22BP), the endogenous inhibitor of the tissue-protective cytokine IL-22. Using mouse models, we demonstrate that IBD development requires T cell-derived IL-22BP. Lastly, intestinal CD4(+) T cells isolated from IBD patients responsive to treatment with antibodies against tumor necrosis factor-alpha (anti-TNF-alpha), the most effective known IBD therapy, exhibited reduced amounts of IL-22BP expression but still expressed IL-22. Our findings suggest that anti-TNF-alpha therapy may act at least in part by suppressing IL-22BP and point toward a more specific potential therapy for IBD.

• 出版日期2016-10-21
• 单位河北医科大学