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
| العنوان: | 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 |
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| المؤلفون: | Julian Parkhill, George Malietzis, Malte Paulsen, Elizabeth Bassity, Paul Scott, Simon T. Peake, Eva Sánchez-Recio, Rakesh Vora, Fahri Bayiroglu, Robin K. S. Phillips, Enrique Montalvillo, Stella C. Knight, José Antonio Garrote, Ailsa Hart, Aravinth U. Murugananthan, Phil Hendy, J. Landy, Simon R. Carding, Luis Fernández-Salazar, Elizabeth R. Mann, Durga Reddi, Yi Harn Siaw, Eduardo Arranz, Nick R. English, Hafid O. Al-Hassi, Ripple Man, Gui H. Lee, David Bernardo, Lydia Durant, Alan W. Walker |
| المساهمون: | Biotechnology and Biological Sciences Research Council (UK), Scottish Government's Rural and Environment Science and Analytical Services, University of Aberdeen, Association for International Cancer Research, Junta de Castilla y León, Wellcome Trust, Parkhill, Julian [0000-0002-7069-5958], Apollo - University of Cambridge Repository, Belirlenecek, Garrote, Jose Antonio -- 0000-0003-1797-6520, Walker, Alan -- 0000-0001-5099-8495 |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname Cellular and Molecular Gastroenterology and Hepatology UVaDOC. Repositorio Documental de la Universidad de Valladolid Cellular and Molecular Gastroenterology and Hepatology, Vol 2, Iss 1, Pp 22-39.e5 (2016) Bernardo, D, Durant, L, Mann, E R, Bassity, E, Montalvillo, E, Man, R, Vora, R, Reddi, D, Bayiroglu, F, Fernández-Salazar, L, English, N R, Peake, S T C, Landy, J, Lee, G H, Malietzis, G, Siaw, Y H, Murugananthan, A U, Hendy, P, Sánchez-Recio, E, Phillips, R K S, Garrote, J A, Scott, P, Parkhill, J, Paulsen, M, Hart, A L, Al-Hassi, H O, Arranz, E, Walker, A W, Carding, S R & Knight, S 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, vol. 2, no. 1, pp. 22-39.e5 . https://doi.org/10.1016/j.jcmgh.2015.08.006 |
| بيانات النشر: | Elsevier BV, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Human Gastrointestinal Tract, 0301 basic medicine, CCR2, Chemokine, Células dendríticas, Human gastrointestinal tract, 3205 Medicina Interna, CCR9, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Treg, regulatory T-cells, Plasmacytoid dendritic cell, Dendritic cells, Proximal colon, pDC, plasmacytoid dendritic cell, Immune tolerance, CCL, chemokine (C-C motif) ligand, PCR, polymerase chain reaction, AMOVA, analysis of molecular variance, DC, dendritic cells, FACS, fluorescence-activated cell sorting, ComputingMilieux_COMPUTERSANDEDUCATION, Mφ, macrophages, CCR, chemokine (C-C motif) receptor, DL, detection limit, Original Research, 2. Zero hunger, mDC, myeloid dendritic cell, education.field_of_study, biology, Microbiota, ILT3, Ig-like transcript 3, Gastroenterology, hemic and immune systems, Proximal Colon, GI, gastrointestinal, 3. Good health, PBMC, peripheral blood mononuclear cells, CFSE, 5-carboxy fluorescein diacetate succinimidyl ester, FITC, fluorescein isothiocyanate, LPMC, lamina propria mononuclear cells, Colon, Population, CD11c, chemical and pharmacologic phenomena, SIRPα, signal regulatory protein α, SPB, sodium phosphate buffer, 03 medical and health sciences, lcsh:RC799-869, Distal Colon, education, Hepatology, Dendritic Cells, Dendritic cell, Molecular biology, IL, interleukin, 030104 developmental biology, RALDH2, retinaldehyde dehydrogenase type 2, Immunology, biology.protein, lcsh:Diseases of the digestive system. Gastroenterology, 3205.03 Gastroenterología, Distal colon |
| الوصف: | Open Access funded by Biotechnology and Biological Sciences Research Council. Under a Creative Commons license.-- et al. [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. This study was funded by the Biotechnology and Biological Sciences Research Council, BBSRC Institute Strategic Programme for Gut Health and Food Safety, grant BB/J004529/1; 16S rRNA gene sequencing was provided by the Wellcome Trust (grant number WT 098051) (to P.S., J.P., A.W.W.); core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (to A.W.W. and the Rowett Institute of Nutrition and Health, University of Aberdeen); the Association for International Cancer Research (AICR), Scotland, grant number 120234 (to H.O.A.); and the Junta de Castilla y León, Spain (SAN196/VA16/07 and SAN196/VA17/07). |
| وصف الملف: | application/pdf |
| تدمد: | 2352-345X |
| DOI: | 10.1016/j.jcmgh.2015.08.006 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe936f722455695677480cbdeeb371d1 https://doi.org/10.1016/j.jcmgh.2015.08.006 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fe936f722455695677480cbdeeb371d1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2352345X |
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| DOI: | 10.1016/j.jcmgh.2015.08.006 |