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Plasmacytoid Dendritic Cells Are Proportionally Expanded at Diagnosis of Type 1 Diabetes and Enhance Islet Autoantigen Presentation to T-Cells Through Immune Complex Capture

OBJECTIVE—Immune-mediated destruction of β-cells resulting in type 1 diabetes involves activation of proinflammatory, islet autoreactive T-cells, a process under the control of dendritic cells of the innate immune system. We tested the hypothesis that type 1 diabetes development is associated with d...

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Autores principales: Allen, Jennifer S., Pang, Karl, Skowera, Ania, Ellis, Richard, Rackham, Chloe, Lozanoska-Ochser, Biliana, Tree, Timothy, Leslie, R. David G., Tremble, Jennifer M., Dayan, Colin M., Peakman, Mark
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606862/
https://www.ncbi.nlm.nih.gov/pubmed/18835928
http://dx.doi.org/10.2337/db08-0964
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author Allen, Jennifer S.
Pang, Karl
Skowera, Ania
Ellis, Richard
Rackham, Chloe
Lozanoska-Ochser, Biliana
Tree, Timothy
Leslie, R. David G.
Tremble, Jennifer M.
Dayan, Colin M.
Peakman, Mark
author_facet Allen, Jennifer S.
Pang, Karl
Skowera, Ania
Ellis, Richard
Rackham, Chloe
Lozanoska-Ochser, Biliana
Tree, Timothy
Leslie, R. David G.
Tremble, Jennifer M.
Dayan, Colin M.
Peakman, Mark
author_sort Allen, Jennifer S.
collection PubMed
description OBJECTIVE—Immune-mediated destruction of β-cells resulting in type 1 diabetes involves activation of proinflammatory, islet autoreactive T-cells, a process under the control of dendritic cells of the innate immune system. We tested the hypothesis that type 1 diabetes development is associated with disturbance of blood dendritic cell subsets that could enhance islet-specific autoimmunity. RESEARCH DESIGN AND METHODS—We examined blood dendritic cells (plasmacytoid and myeloid) in 40 patients with recent-onset diabetes (median duration 28 days) and matched control subjects. We also examined the relative ability of different dendritic cell subsets to process and present soluble or immune complexed islet cell autoantigen (the islet tyrosine phosphatase IA-2) to responder CD4 T-cells. RESULTS—The balance of blood dendritic cells was profoundly disturbed at diabetes diagnosis, with a significantly elevated proportion of plasmacytoid and reduction of myeloid cells compared with control subjects. Dendritic cell subset distribution was normal in long-standing disease and in patients with type 2 diabetes. Both dendritic cell subsets processed and presented soluble IA-2 to CD4 T-cells after short-term culture, but only plasmacytoid dendritic cells enhanced (by as much as 100%) autoantigen presentation in the presence of IA-2(+) autoantibody patient serum. CONCLUSIONS—The plasmacytoid subset of dendritic cells is overrepresented in the blood close to diabetes onset and shows a distinctive ability to capture islet autoantigenic immune complexes and enhance autoantigen-driven CD4 T-cell activation. This suggests a synergistic proinflammatory role for plasmacytoid dendritic cells and islet cell autoantibodies in type 1 diabetes.
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spelling pubmed-26068622010-01-01 Plasmacytoid Dendritic Cells Are Proportionally Expanded at Diagnosis of Type 1 Diabetes and Enhance Islet Autoantigen Presentation to T-Cells Through Immune Complex Capture Allen, Jennifer S. Pang, Karl Skowera, Ania Ellis, Richard Rackham, Chloe Lozanoska-Ochser, Biliana Tree, Timothy Leslie, R. David G. Tremble, Jennifer M. Dayan, Colin M. Peakman, Mark Diabetes Immunology and Transplantation OBJECTIVE—Immune-mediated destruction of β-cells resulting in type 1 diabetes involves activation of proinflammatory, islet autoreactive T-cells, a process under the control of dendritic cells of the innate immune system. We tested the hypothesis that type 1 diabetes development is associated with disturbance of blood dendritic cell subsets that could enhance islet-specific autoimmunity. RESEARCH DESIGN AND METHODS—We examined blood dendritic cells (plasmacytoid and myeloid) in 40 patients with recent-onset diabetes (median duration 28 days) and matched control subjects. We also examined the relative ability of different dendritic cell subsets to process and present soluble or immune complexed islet cell autoantigen (the islet tyrosine phosphatase IA-2) to responder CD4 T-cells. RESULTS—The balance of blood dendritic cells was profoundly disturbed at diabetes diagnosis, with a significantly elevated proportion of plasmacytoid and reduction of myeloid cells compared with control subjects. Dendritic cell subset distribution was normal in long-standing disease and in patients with type 2 diabetes. Both dendritic cell subsets processed and presented soluble IA-2 to CD4 T-cells after short-term culture, but only plasmacytoid dendritic cells enhanced (by as much as 100%) autoantigen presentation in the presence of IA-2(+) autoantibody patient serum. CONCLUSIONS—The plasmacytoid subset of dendritic cells is overrepresented in the blood close to diabetes onset and shows a distinctive ability to capture islet autoantigenic immune complexes and enhance autoantigen-driven CD4 T-cell activation. This suggests a synergistic proinflammatory role for plasmacytoid dendritic cells and islet cell autoantibodies in type 1 diabetes. American Diabetes Association 2009-01 /pmc/articles/PMC2606862/ /pubmed/18835928 http://dx.doi.org/10.2337/db08-0964 Text en Copyright © 2009, American Diabetes Association Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Immunology and Transplantation
Allen, Jennifer S.
Pang, Karl
Skowera, Ania
Ellis, Richard
Rackham, Chloe
Lozanoska-Ochser, Biliana
Tree, Timothy
Leslie, R. David G.
Tremble, Jennifer M.
Dayan, Colin M.
Peakman, Mark
Plasmacytoid Dendritic Cells Are Proportionally Expanded at Diagnosis of Type 1 Diabetes and Enhance Islet Autoantigen Presentation to T-Cells Through Immune Complex Capture
title Plasmacytoid Dendritic Cells Are Proportionally Expanded at Diagnosis of Type 1 Diabetes and Enhance Islet Autoantigen Presentation to T-Cells Through Immune Complex Capture
title_full Plasmacytoid Dendritic Cells Are Proportionally Expanded at Diagnosis of Type 1 Diabetes and Enhance Islet Autoantigen Presentation to T-Cells Through Immune Complex Capture
title_fullStr Plasmacytoid Dendritic Cells Are Proportionally Expanded at Diagnosis of Type 1 Diabetes and Enhance Islet Autoantigen Presentation to T-Cells Through Immune Complex Capture
title_full_unstemmed Plasmacytoid Dendritic Cells Are Proportionally Expanded at Diagnosis of Type 1 Diabetes and Enhance Islet Autoantigen Presentation to T-Cells Through Immune Complex Capture
title_short Plasmacytoid Dendritic Cells Are Proportionally Expanded at Diagnosis of Type 1 Diabetes and Enhance Islet Autoantigen Presentation to T-Cells Through Immune Complex Capture
title_sort plasmacytoid dendritic cells are proportionally expanded at diagnosis of type 1 diabetes and enhance islet autoantigen presentation to t-cells through immune complex capture
topic Immunology and Transplantation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606862/
https://www.ncbi.nlm.nih.gov/pubmed/18835928
http://dx.doi.org/10.2337/db08-0964
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