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

Ehud Zigmond, Chen Varol, Julia Farache, Elinor Elmaliah, Ansuman T. Satpathy, Gilgi Friedlander, Matthias Mack, Nahum Shpigel, Ivo G. Boneca, Kenneth M. Murphy, Guy Shakhar, Zamir Halpern, Steffen Jung

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385 Scopus citations

Abstract

Ly6Chi monocytes seed the healthy intestinal lamina propria to give rise to resident CX3CR1+ 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 Ly6Chi 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 Ly6Chi 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 Ly6Chi monocytes, marking them as potential targets for inflammatory bowel disease (IBD) therapy.

Original languageEnglish
Pages (from-to)1076-1090
Number of pages15
JournalImmunity
Volume37
Issue number6
DOIs
StatePublished - Dec 14 2012

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    Zigmond, E., Varol, C., Farache, J., Elmaliah, E., Satpathy, A. T., Friedlander, G., Mack, M., Shpigel, N., Boneca, I. G., Murphy, K. M., Shakhar, G., Halpern, Z., & Jung, S. (2012). Ly6Chi Monocytes in the Inflamed Colon Give Rise to Proinflammatory Effector Cells and Migratory Antigen-Presenting Cells. Immunity, 37(6), 1076-1090. https://doi.org/10.1016/j.immuni.2012.08.026