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 Mark ORCID: https://orcid.org/0000-0002-6557-3462 and Peakman, Mark 2009. Plasmacytoid dendritic cells are proportionally expanded at diagnosis of Type 1 diabetes and enhance islet autoantigen presentation to T-cells through immune complex capture. Diabetes 58 (1) , pp. 138-145. 10.2337/db08-0964

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	American Diabetes Association
ISSN:	0012-1797
Last Modified:	20 Oct 2022 08:57
URI:	https://orca.cardiff.ac.uk/id/eprint/30160

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