Chemokine (C-C Motif) Receptor 2 mediates dendritic cell recruitment to the human colon but is not responsible for differences observed in dendritic cell subsets, phenotype, and function between the proximal and distal colon

Bernardo, David, Durant, Lydia, Mann, Elizabeth R., Bassity, Elizabeth, Montalvillo, Enrique, Man, Ripple, Vora, Rakesh, Reddi, Durga, Bayiroglu, Fahri, Fernández-Salazar, Luis, English, Nick. R., Peake, Simon T.C., Landy, Jon, Lee, Gui. H., Malietzis, George, Siaw, Yi Harn, Murugananthan, Aravinth U., Hendy, Phil, Sánchez-Recio, Eva, Phillips, Robin K.S., Garrote, Jose A., Scott, Paul, Parkhill, Julian, Paulsen, Malte, Hart, Ailsa L., Al-Hassi, Hafid O., Arranz, Eduardo, Walker, Alan W., Carding, Simon R. and Knight, Stella C. (2016) Chemokine (C-C Motif) Receptor 2 mediates dendritic cell recruitment to the human colon but is not responsible for differences observed in dendritic cell subsets, phenotype, and function between the proximal and distal colon. Cellular and Molecular Gastroenterology and Hepatology, 2 (1). 22-39.e5. ISSN 2352-345X

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Abstract

Background & Aims: Most knowledge about gastrointestinal (GI)-tract dendritic cells (DC) relies on murine studies where CD103+ DC specialize in generating immune tolerance with the functionality of CD11b+/− subsets being unclear. Information about human GI-DC is scarce, especially regarding regional specifications. Here, we characterized human DC properties throughout the human colon. Methods: Paired proximal (right/ascending) and distal (left/descending) human colonic biopsies from 95 healthy subjects were taken; DC were assessed by flow cytometry and microbiota composition assessed by 16S rRNA gene sequencing. Results: Colonic DC identified were myeloid (mDC, CD11c+CD123−) and further divided based on CD103 and SIRPα (human analog of murine CD11b) expression. CD103-SIRPα+ DC were the major population and with CD103+SIRPα+ DC were CD1c+ILT3+CCR2+ (although CCR2 was not expressed on all CD103+SIRPα+ DC). CD103+SIRPα- DC constituted a minor subset that were CD141+ILT3−CCR2−. Proximal colon samples had higher total DC counts and fewer CD103+SIRPα+ cells. Proximal colon DC were more mature than distal DC with higher stimulatory capacity for CD4+CD45RA+ T-cells. However, DC and DC-invoked T-cell expression of mucosal homing markers (β7, CCR9) was lower for proximal DC. CCR2 was expressed on circulating CD1c+, but not CD141+ mDC, and mediated DC recruitment by colonic culture supernatants in transwell assays. Proximal colon DC produced higher levels of cytokines. Mucosal microbiota profiling showed a lower microbiota load in the proximal colon, but with no differences in microbiota composition between compartments. Conclusions: Proximal colonic DC subsets differ from those in distal colon and are more mature. Targeted immunotherapy using DC in T-cell mediated GI tract inflammation may therefore need to reflect this immune compartmentalization.

Item Type:	Article
Uncontrolled Keywords:	ccr2,dendritic cells,distal colon,human gastrointestinal tract,proximal colon,microbiota,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User:	Pure Connector
Date Deposited:	06 Jan 2016 16:01
Last Modified:	22 Oct 2022 00:32
URI:	https://ueaeprints.uea.ac.uk/id/eprint/56098
DOI:	10.1016/j.jcmgh.2015.08.006

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