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

Overview

Journal Cell Mol Gastroenterol Hepatol

Specialty Gastroenterology

Date 2016 Feb 12

PMID 26866054

Citations 18

Authors

David Bernardo

Lydia Durant

Elizabeth R Mann

Elizabeth Bassity

Enrique Montalvillo

Ripple Man

Rakesh Vora

Durga Reddi

Fahri Bayiroglu

Luis Fernandez-Salazar

Nick R English

Simon T C Peake

Jon Landy

Gui H Lee

George Malietzis

Yi Harn Siaw

Aravinth U Murugananthan

Phil Hendy

Eva Sanchez-Recio

Robin K S Phillips

Jose A Garrote

Paul Scott

Julian Parkhill

Malte Paulsen

Ailsa L Hart

Hafid O Al-Hassi

Eduardo Arranz

Alan W Walker

Simon R Carding

Stella C Knight

Affiliations

Soon will be listed here.

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, CD11cCD123) and further divided based on CD103 and SIRPα (human analog of murine CD11b) expression. CD103SIRPα DC were the major population and with CD103SIRPα DC were CD1cILT3CCR2 (although CCR2 was not expressed on all CD103SIRPα DC). CD103SIRPα DC constituted a minor subset that were CD141ILT3CCR2. Proximal colon samples had higher total DC counts and fewer CD103SIRPα cells. Proximal colon DC were more mature than distal DC with higher stimulatory capacity for CD4CD45RA 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.

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