Expression of the Atypical Chemokine Receptor ACKR4 Identifies a Novel Population of Intestinal Submucosal Fibroblasts That Preferentially Expresses Endothelial Cell Regulators

The Journal of Immunology : Official Journal of the American Association of Immunologists
Carolyn A ThomsonRobert J B Nibbs

Abstract

Atypical chemokine receptors (ACKRs) are expressed by discrete populations of stromal cells at specific anatomical locations where they control leukocyte migration by scavenging or transporting chemokines. ACKR4 is an atypical receptor for CCL19, CCL21, and CCL25. In skin, ACKR4 plays indispensable roles in regulating CCR7-dependent APC migration, and there is a paucity of migratory APCs in the skin-draining lymph nodes of Ackr4-deficient mice under steady-state and inflammatory conditions. This is caused by loss of ACKR4-mediated CCL19/21 scavenging by keratinocytes and lymphatic endothelial cells. In contrast, we show in this study that Ackr4 deficiency does not affect dendritic cell abundance in the small intestine and mesenteric lymph nodes, at steady state or after R848-induced mobilization. Moreover, Ackr4 expression is largely restricted to mesenchymal cells in the intestine, where it identifies a previously uncharacterized population of fibroblasts residing exclusively in the submucosa. Compared with related Ackr4- mesenchymal cells, these Ackr4+ fibroblasts have elevated expression of genes encoding endothelial cell regulators and lie in close proximity to submucosal blood and lymphatic vessels. We also provide evidenc...Continue Reading

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Citations

Dec 17, 2019·Journal of Leukocyte Biology·Nadine EckertReinhold Förster
Sep 5, 2020·Nature Cell Biology·Neil McCarthyRamesh A Shivdasani
Mar 18, 2020·Immunology·Carolyn A ThomsonAllan Mcl Mowat
Feb 22, 2021·Biochemical and Biophysical Research Communications·Min ZhangXiang Cheng
Apr 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Cameron R BastowIain Comerford
Jun 9, 2021·Life Sciences·Mostafa M MohammedMohamed F Abed El Baky

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