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 ColonSummary
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+/â subsets being unclear. Information about human GI-DC is scarce, especially regarding regi...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X15001514 |
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doaj-43a045023eba4751af960d5f5612c1ab |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
David Bernardo Lydia Durant Elizabeth R. Mann Elizabeth Bassity Enrique Montalvillo Ripple Man Rakesh Vora Durga Reddi Fahri Bayiroglu Luis Fernández-Salazar Nick R. English Simon T.C. Peake Jon Landy Gui H. Lee George Malietzis Yi Harn Siaw Aravinth U. Murugananthan Phil Hendy Eva Sánchez-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 |
| spellingShingle |
David Bernardo Lydia Durant Elizabeth R. Mann Elizabeth Bassity Enrique Montalvillo Ripple Man Rakesh Vora Durga Reddi Fahri Bayiroglu Luis Fernández-Salazar Nick R. English Simon T.C. Peake Jon Landy Gui H. Lee George Malietzis Yi Harn Siaw Aravinth U. Murugananthan Phil Hendy Eva Sánchez-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 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 ColonSummary Cellular and Molecular Gastroenterology and Hepatology |
| author_facet |
David Bernardo Lydia Durant Elizabeth R. Mann Elizabeth Bassity Enrique Montalvillo Ripple Man Rakesh Vora Durga Reddi Fahri Bayiroglu Luis Fernández-Salazar Nick R. English Simon T.C. Peake Jon Landy Gui H. Lee George Malietzis Yi Harn Siaw Aravinth U. Murugananthan Phil Hendy Eva Sánchez-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 |
| author_sort |
David Bernardo |
| title |
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 ColonSummary |
| title_short |
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 ColonSummary |
| title_full |
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 ColonSummary |
| title_fullStr |
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 ColonSummary |
| title_full_unstemmed |
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 ColonSummary |
| title_sort |
chemokine (c-c motif) receptor 2 mediates dendritic cellâ recruitment to the human colon but is not responsibleâ forâ differences observed in dendritic cellâ subsets,â phenotype, and function between the proximalâ andâ distal colonsummary |
| publisher |
Elsevier |
| series |
Cellular and Molecular Gastroenterology and Hepatology |
| issn |
2352-345X |
| publishDate |
2016-01-01 |
| description |
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+/â 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+CD123â) 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+ILT3âCCR2â. 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. Keywords: CCR2, Dendritic Cells, Distal Colon, Human Gastrointestinal Tract, Proximal Colon, Microbiota |
| url |
http://www.sciencedirect.com/science/article/pii/S2352345X15001514 |
| work_keys_str_mv |
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doaj-43a045023eba4751af960d5f5612c1ab2020-11-24T21:43:41ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2016-01-01212239.e5Chemokine (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 ColonSummaryDavid Bernardo0Lydia Durant1Elizabeth R. Mann2Elizabeth Bassity3Enrique Montalvillo4Ripple Man5Rakesh Vora6Durga Reddi7Fahri Bayiroglu8Luis Fernández-Salazar9Nick R. English10Simon T.C. Peake11Jon Landy12Gui H. Lee13George Malietzis14Yi Harn Siaw15Aravinth U. Murugananthan16Phil Hendy17Eva Sánchez-Recio18Robin K.S. Phillips19Jose A. Garrote20Paul Scott21Julian Parkhill22Malte Paulsen23Ailsa L. Hart24Hafid O. Al-Hassi25Eduardo Arranz26Alan W. Walker27Simon R. Carding28Stella C. Knight29Antigen Presentation Research Group, Imperial College London, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United Kingdom; Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomGut Health and Food Safety Programme, Institute of Food Research, Norwich, United KingdomMucosal Immunology Group, Instituto de BiologÃa y Genética Molecular (IBGM), Universidad de ValladolidâCSIC, Valladolid, SpainSt. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United Kingdom; St. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United KingdomDepartment of Physiology, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey; Faculty of Farmacy, Agri Ä°brahim Cecen University, Agri, TurkeyGastroenterology Service, Hospital ClÃnico Universitario de Valladolid, Valladolid, SpainAntigen Presentation Research Group, Imperial College London, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United Kingdom; St. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United Kingdom; St. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United Kingdom; St. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United Kingdom; St. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United Kingdom; St. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United Kingdom; St. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United Kingdom; St. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United KingdomSt. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomMucosal Immunology Group, Instituto de BiologÃa y Genética Molecular (IBGM), Universidad de ValladolidâCSIC, Valladolid, Spain; Genetics and Molecular Biology Department, Clinical Laboratory Service, Hospital Universitario Rio Hortega, Valladolid, SpainPathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United KingdomPathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United KingdomNational Heart and Lung Institute, Imperial College London, LondonSt. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United KingdomSt. Markâs Hospital, North West London Hospitals NHS Trust, Harrow, United KingdomPathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom; Microbiology Group, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United KingdomGut Health and Food Safety Programme, Institute of Food Research, Norwich, United Kingdom; Norwich Medical School, University of East Anglia, Norwich, United KingdomAntigen Presentation Research Group, Imperial College London, Harrow, United Kingdom; Correspondence Address correspondence to: Stella C. Knight, PhD, Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Markâs Campus, Watford Road, Harrow, HA1 3UJ, United Kingdom. fax: +44 (0) 20 8869 3532.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+/â 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+CD123â) 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+ILT3âCCR2â. 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. Keywords: CCR2, Dendritic Cells, Distal Colon, Human Gastrointestinal Tract, Proximal Colon, Microbiotahttp://www.sciencedirect.com/science/article/pii/S2352345X15001514 |