Inflammation triggers immediate rather than progressive changes in monocyte differentiation in the small intestine

Girmay Desalegn and Oliver Pabst ()
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Girmay Desalegn: RWTH Aachen University
Oliver Pabst: RWTH Aachen University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Bone marrow-derived circulating monocytes contribute to the replenishment and maintenance of the intestinal macrophage population. Intestinal monocytes undergo context-dependent phenotypic and functional adaptations to either maintain local immune balance or support intestinal inflammation. Here we use monocyte adoptive transfer to dissect the dynamics of monocyte-to-macrophage differentiation in normal and inflamed small intestine. We find that during homeostasis CCR2 and β7-integrin mediate constitutive homing of monocytes to the gut. By contrast, intestinal inflammation increases monocyte recruitment via CCR2, but not β7-integrin. In the non-inflamed intestine, monocytes gradually differentiate to express genes typically associated with tolerogenic macrophage functions. Conversely, immediately upon entry into the inflamed intestine, monocytes adapt a different expression pattern in a partly Trem-1-dependent manner. Our observations suggest that inflammation fundamentally changes the kinetics and modalities of monocyte differentiation in tissues.

Date: 2019
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DOI: 10.1038/s41467-019-11148-2

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