Intestinal CD169+ macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes

被引：194

作者：

Asano, Kenichi ^{[1
,2
]}

Takahashi, Naomichi ^{[1
]}

Ushiki, Mikiko ^{[1
]}

Monya, Misa ^{[1
]}

Aihara, Fumiaki ^{[1
]}

Kuboki, Erika ^{[1
]}

Moriyama, Shigetaka ^{[1
]}

Iida, Mayumi ^{[1
]}

Kitamura, Hiroshi ^{[3
]}

Qiu, Chun-Hong ^{[4
]}

Watanabe, Takashi ^{[5
]}

Tanaka, Masato ^{[1
]}

机构：

[1] Tokyo Univ Pharm & Life Sci, Sch Life Sci, Lab Immune Regulat, Hachioji, Tokyo 1920392, Japan

[2] PRESTO, Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan

[3] Rakuno Gakuen Univ, Sch Vet Med, Vet Physiol Lab, Ebetsu, Hokkaido 0698501, Japan

[4] Shandong Univ, Inst Cell Biol, Sch Med, Jinan 250012, Shandong, Peoples R China

[5] RIKEN, Ctr Integrated Med Sci, Immunogen Lab, Yokohama, Kanagawa 2270045, Japan

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

INNATE LYMPHOID-CELLS; ROR-GAMMA-T; DENDRITIC CELLS; LY6C(HI) MONOCYTES; EXPRESSION; PATHOGENESIS; INVOLVEMENT; HOMEOSTASIS; LYMPHOCYTES; GENERATION;

D O I：

10.1038/ncomms8802

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Lamina propria (LP) macrophages are constantly exposed to commensal bacteria, and are refractory to those antigens in an interleukin (IL)-10-dependent fashion. However, the mechanisms that discriminate hazardous invasion by bacteria from peaceful co-existence with them remain elusive. Here we show that CD169(+) macrophages reside not at the villus tip, but at the bottom-end of the LP microenvironment. Following mucosal injury, the CD169(+) macrophages recruit inflammatory monocytes by secreting CCL8. Selective depletion of CD169(+) macrophages or administration of neutralizing anti-CCL8 antibody ameliorates the symptoms of experimentally induced colitis in mice. Collectively, we identify an LP-resident macrophage subset that links mucosal damage and inflammatory monocyte recruitment. Our results suggest that CD169(+) macrophage-derived CCL8 serves as an emergency alert for the collapse of barrier defence, and is a promising target for the suppression of mucosal injury.

引用

页数：14

共 57 条

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