TY - JOUR
T1 - Ly6Chi Monocytes in the Inflamed Colon Give Rise to Proinflammatory Effector Cells and Migratory Antigen-Presenting Cells
AU - Zigmond, Ehud
AU - Varol, Chen
AU - Farache, Julia
AU - Elmaliah, Elinor
AU - Satpathy, Ansuman T.
AU - Friedlander, Gilgi
AU - Mack, Matthias
AU - Shpigel, Nahum
AU - Boneca, Ivo G.
AU - Murphy, Kenneth M.
AU - Shakhar, Guy
AU - Halpern, Zamir
AU - Jung, Steffen
PY - 2012/12/14
Y1 - 2012/12/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84870900504&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2012.08.026
DO - 10.1016/j.immuni.2012.08.026
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C2 - 23219392
AN - SCOPUS:84870900504
SN - 1074-7613
VL - 37
SP - 1076
EP - 1090
JO - Immunity
JF - Immunity
IS - 6
ER -