title: Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells.
abstract: 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.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Zigmond
authors.forename: Chen
authors.initials: C
authors.lastname: Varol
authors.forename: Julia
authors.initials: J
authors.lastname: Farache
authors.forename: Elinor
authors.initials: E
authors.lastname: Elmaliah
authors.forename: Ansuman T
authors.initials: AT
authors.lastname: Satpathy
authors.forename: Gilgi
authors.initials: G
authors.lastname: Friedlander
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.forename: Nahum
authors.initials: N
authors.lastname: Shpigel
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Boneca
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Guy
authors.initials: G
authors.lastname: Shakhar
authors.forename: Zamir
authors.initials: Z
authors.lastname: Halpern
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000276:immunology*; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D016130:Immunophenotyping; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology / Q000378:metabolism; D054390:Receptors, CCR2 / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; C494192:Ly-6C antigen, mouse; D053473:Nod2 Signaling Adaptor Protein; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D051195:Toll-Like Receptor 2