Details

Autor(en) / Beteiligte

• Yamaguchi, Toshio
• Iijima, Hideki
• Yoshihara, Takeo
• Tani, Mizuki
• Otake, Yuriko
• Iwatani, Shuko
• Amano, Takahiro
• Tashiro, Taku
• Kurahashi, Tomohide
• Inoue, Takanori
• Tsujii, Yoshiki
• Hayashi, Yoshito
• Inoue, Takahiro
• Motooka, Daisuke
• Nakamura, Shota
• Shinzaki, Shinichiro
• Takehara, Tetsuo

Titel

Exacerbation of non‐steroidal anti‐inflammatory drug‐induced enteropathy in C‐C chemokine receptor type 7‐deficient mice

Ist Teil von

• Journal of gastroenterology and hepatology, 2022-08, Vol.37 (8), p.1561-1570

Ort / Verlag

Australia: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Wiley Online Library

Beschreibungen/Notizen

• Background and Aim Non‐steroidal anti‐inflammatory drugs (NSAIDs) induce intestinal enteropathy and the pathophysiology is related to immune‐mediated mechanisms. We aimed to investigate the role of C‐C chemokine receptor type 7 (CCR7) which regulates immune cell migration in NSAID‐induced enteropathy. Methods Injury of the small intestine was evaluated 24 h after the subcutaneous injection of indomethacin in CCR7‐deficient (Ccr7−/−) and wild‐type (WT) mice. The cellular profile and cytokine production in intestinal cells were analyzed. Indomethacin‐induced enteropathy was evaluated in mice adoptively transferred with CD103+ dendritic cells (DCs) from Ccr7−/− or WT mice. Results Indomethacin induced more severe intestinal injury in Ccr7−/− mice than in WT mice. The major inflammatory cytokines were not increased and the proportion of regulatory T cells following indomethacin injection was not decreased in Ccr7−/− mice compared with WT mice. The expression of interleukin (IL)‐22 binding protein (IL‐22BP), which inhibits IL‐22 activity, was significantly higher in CD103+ DCs from Ccr7−/− mice than those from WT mice. Mice adoptively transferred with CD103+ DCs isolated from Ccr7−/− mice exhibited more severe intestinal injury following indomethacin injection compared with those adoptively transferred with CD103+ DCs of WT mice. Ccr7−/− mice injected with indomethacin showed a significant reduction in regenerating islet‐derived 1 (Reg1) mRNA expression, which is regulated by IL‐22, in intestinal epithelial cells. Conclusions C‐C chemokine receptor type 7 deficiency exacerbated NSAID‐induced enteropathy in association with an altered phenotype of CD103+ DCs that produces IL‐22BP. CCR7 contributes to protect the small intestine from NSAID‐induced mucosal injury.