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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\u2212 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 evidence that Ackr4+ fibroblasts form physical interactions with lymphatic endothelial cells, and engage in molecular interactions with these cells via the VEGFD\/VEGFR3 and CCL21\/ACKR4 pathways. Thus, intestinal submucosal fibroblasts in mice are a distinct population of intestinal mesenchymal cells that can be identified by their expression of Ackr4 and have transcriptional and anatomical properties that strongly suggest roles in endothelial cell regulation.<\/jats:p>","DOI":"10.4049\/jimmunol.1700967","type":"journal-article","created":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T15:15:18Z","timestamp":1526310918000},"page":"215-229","source":"Crossref","is-referenced-by-count":40,"title":["Expression of the Atypical Chemokine Receptor ACKR4 Identifies a Novel Population of Intestinal Submucosal Fibroblasts That Preferentially Expresses Endothelial Cell Regulators"],"prefix":"10.1093","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3906-7539","authenticated-orcid":false,"given":"Carolyn A","family":"Thomson","sequence":"first","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow , Glasgow G12 8TA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7147-4380","authenticated-orcid":false,"given":"Serge A","family":"van de Pavert","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Aix Marseille Universit\u00e9, CNRS, INSERM , 13288 Marseille Cedex 9 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4086-0289","authenticated-orcid":false,"given":"Michelle","family":"Stakenborg","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, Catholic University Leuven , BE-3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien","family":"Labeeuw","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, Catholic University Leuven , BE-3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2902-4976","authenticated-orcid":false,"given":"Gianluca","family":"Matteoli","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, Catholic University Leuven , BE-3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9389-3079","authenticated-orcid":false,"given":"Allan McI","family":"Mowat","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow , Glasgow G12 8TA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8150-0044","authenticated-orcid":false,"given":"Robert J B","family":"Nibbs","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow , Glasgow G12 8TA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,7,1]]},"reference":[{"key":"2025030417565784000_r1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1146\/annurev.physiol.70.113006.100646","article-title":"Mesenchymal cells of the intestinal lamina propria","volume":"73","author":"Powell","year":"2011","journal-title":"Annu. 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