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

被引：0

作者：

Yamaguchi, Toshio ^{[1
,2
]}

Iijima, Hideki ^{[1
]}

Yoshihara, Takeo ^{[1
]}

Tani, Mizuki ^{[1
]}

Otake, Yuriko ^{[1
]}

Iwatani, Shuko ^{[1
]}

Amano, Takahiro ^{[1
]}

Tashiro, Taku ^{[1
]}

Kurahashi, Tomohide ^{[1
]}

Inoue, Takanori ^{[1
]}

Tsujii, Yoshiki ^{[1
]}

Hayashi, Yoshito ^{[1
]}

Inoue, Takahiro ^{[1
]}

Motooka, Daisuke ^{[3
]}

Nakamura, Shota ^{[3
]}

Shinzaki, Shinichiro ^{[1
]}

Takehara, Tetsuo ^{[1
]}

机构：

[1] Osaka Univ, Dept Gastroenterol & Hepatol, Grad Sch Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan

[2] Osaka Rosai Hosp, Dept Gastroenterol, Osaka, Japan

[3] Osaka Univ, Res Inst Microbial Dis, Dept Infect Metagen, Osaka, Japan

来源：

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY | 2022年 / 37卷 / 08期

基金：

日本学术振兴会;

关键词：

IL-22 binding protein; migration; NSAIDs C-C chemokine receptor type 7; LYMPHOID-TISSUE CHEMOKINE; T-CELL; DENDRITIC CELLS; SMALL-INTESTINE; LAMINA PROPRIA; BINDING-PROTEIN; CCR7; IL-22; INFLAMMATION; IMMUNITY;

D O I：

10.1111/jgh.15868

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：1561 / 1570

页数：10

共 46 条

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