Ly6Chi Monocytes in the Inflamed Colon Give Rise to Proinflammatory Effector Cells and Migratory Antigen-Presenting Cells

被引：572

作者：

Zigmond, Ehud ^{[1
,3
,4
]}

Varol, Chen ^{[3
,4
]}

Farache, Julia ^{[1
]}

Elmaliah, Elinor ^{[3
,4
]}

Satpathy, Ansuman T. ^{[5
]}

Friedlander, Gilgi ^{[2
]}

Mack, Matthias ^{[6
]}

Shpigel, Nahum ^{[7
]}

Boneca, Ivo G. ^{[8
,9
]}

Murphy, Kenneth M. ^{[5
]}

Shakhar, Guy ^{[1
]}

Halpern, Zamir ^{[3
,4
]}

Jung, Steffen ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel

[2] Weizmann Inst Sci, Dept Biol Serv, IL-76100 Rehovot, Israel

[3] Tel Aviv Univ, Sourasky Med Ctr, Res Ctr Digest Tract & Liver Dis, IL-64239 Tel Aviv, Israel

[4] Tel Aviv Univ, Sackler Fac Med, IL-64239 Tel Aviv, Israel

[5] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA

[6] Univ Regensburg, Dept Internal Med, D-93042 Regensburg, Germany

[7] Hebrew Univ Jerusalem, Koret Sch Vet Med, Fac Agr, IL-76100 Rehovot, Israel

[8] Inst Pasteur, Grp Biol & Genet Bacterial Cell Wall, F-75015 Paris, France

[9] INSERM, Grp Avenir, F-75015 Paris, France

来源：

IMMUNITY | 2012年 / 37卷 / 06期

基金：

欧洲研究理事会; 欧盟第七框架计划;

关键词：

CD103(+) DENDRITIC CELLS; REGULATORY T-CELLS; INTESTINAL HOMEOSTASIS; EXPERIMENTAL COLITIS; BACTERIAL-INFECTION; LAMINA-PROPRIA; MACROPHAGES; INFLAMMATION; MICE; RECOGNITION;

D O I：

10.1016/j.immuni.2012.08.026

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Ly6C(hi) monocytes seed the healthy intestinal lamina propria to give rise to resident CX(3)CR1(+) macrophages that contribute to the maintenance of gut homeostasis. Here we report on two alternative monocyte fates in the inflamed colon. We showed that CCR2 expression is essential to the recruitment of Ly6C(hi) monocytes to the inflamed gut to become the dominant mononuclear cell type in the lamina propria during settings of acute colitis. In the inflammatory microenvironment, monocytes upregulated TLR2 and NOD2, rendering them responsive to bacterial products to become proinflammatory effector cells. Ablation of Ly6C(hi) monocytes ameliorated acute gut inflammation. With time, monocytes differentiated into migratory antigen-presenting cells capable of priming naive T cells, thus acquiring hallmarks reminiscent of dendritic cells. Collectively, our results highlight cellular dynamics in the inflamed colon and the plasticity of Ly6C(hi) monocytes, marking them as potential targets for inflammatory bowel disease (IBD) therapy.

引用

页码：1076 / 1090

页数：15