Imperial College London
Alternate

ProfessorStellaKnight

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Research Investigator
 
 
 
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Contact

 

+44 (0)20 8869 3494s.knight Website

 
 
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Assistant

 

Ms Alison Scoggins +44 (0)20 8869 3534

 
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Location

 

7W032Northwick ParkNorthwick Park and St Marks Site

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Summary

 

Publications

Citation

BibTex format

@article{Bernardo:2015:10.1016/j.jcmgh.2015.08.006,
author = {Bernardo, D and Mann, ER and Montalvillo, E and Bassity, E and Bayiroglu, F and Man, R and Fernández-Salazar, L and English, NR and Peake, STC and Landy, J and Lee, GH and Malietzis, G and Siaw, YH and Vora, R and Murugananthan, A and Sánchez-Recio, E and Phillips, RKS and Garrote, JA and Scott, P and Parkhill, J and Hart, AL and Omar, HO and Arranz, E and Walker, AW and Carding, SR and Knight, SC},
doi = {10.1016/j.jcmgh.2015.08.006},
journal = {Cellular and Molecular Gastroenterology and Hepatology},
pages = {22--39.e5},
title = {CCR2 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},
url = {http://dx.doi.org/10.1016/j.jcmgh.2015.08.006},
volume = {2},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background & aimsMost 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.MethodsPaired 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.ResultsColonic 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.ConclusionsProximal colonic DC subsets differ from those in distal colon being more mature. Targeted immunotherapy using DC in T-cell mediated GI-tract inflammation may therefore need to reflect this immune compartmentalization.
AU  - Bernardo,D
AU  - Mann,ER
AU  - Montalvillo,E
AU  - Bassity,E
AU  - Bayiroglu,F
AU  - Man,R
AU  - Fernández-Salazar,L
AU  - English,NR
AU  - Peake,STC
AU  - Landy,J
AU  - Lee,GH
AU  - Malietzis,G
AU  - Siaw,YH
AU  - Vora,R
AU  - Murugananthan,A
AU  - Sánchez-Recio,E
AU  - Phillips,RKS
AU  - Garrote,JA
AU  - Scott,P
AU  - Parkhill,J
AU  - Hart,AL
AU  - Omar,HO
AU  - Arranz,E
AU  - Walker,AW
AU  - Carding,SR
AU  - Knight,SC
DO  - 10.1016/j.jcmgh.2015.08.006
EP  - 39
PY  - 2015///
SN  - 2352-345X
SP  - 22
TI  - CCR2 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
T2  - Cellular and Molecular Gastroenterology and Hepatology
UR  - http://dx.doi.org/10.1016/j.jcmgh.2015.08.006
UR  - http://hdl.handle.net/10044/1/26031
VL  - 2
ER  -
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