Viral infection prevents diabetes by inducing regulatory T cells through NKT cellâ plasmacytoid dendritic cell interplay

Hdl Handle:
http://hdl.handle.net/10675.2/664
Title:
Viral infection prevents diabetes by inducing regulatory T cells through NKT cellâ plasmacytoid dendritic cell interplay
Authors:
Diana, Julien ( 0000-0001-7542-042X ) ; Brezar, Vedran; Beaudoin, Lucie; Dalod, Marc ( 0000-0002-6436-7966 ) ; Mellor, Andrew L.; Tafuri, Anna; von Herrath, Matthias; Boitard, Christian ( 0000-0003-3076-6966 ) ; Mallone, Roberto; Lehuen, Agnes
Abstract:
Type 1 diabetes (T1D) is an autoimmune disease resulting from T cellâ mediated destruction of insulin-producing β cells, and viral infections can prevent the onset of disease. Invariant natural killer T cells (iNKT cells) exert a regulatory role in T1D by inhibiting autoimmune T cell responses. As iNKT cellâ plasmacytoid dendritic cell (pDC) cooperation controls viral replication in the pancreatic islets, we investigated whether this cellular cross talk could interfere with T1D development during viral infection. Using both virus-induced and spontaneous mouse models of T1D, we show that upon viral infection, iNKT cells induce TGF-βâ producing pDCs in the pancreatic lymph nodes (LNs). These tolerogenic pDCs convert naive anti-islet T cells into Foxp3+ CD4+ regulatory T cells (T reg cells) in pancreatic LNs. T reg cells are then recruited into the pancreatic islets where they produce TGF-β, which dampens the activity of viral- and islet-specific CD8+ T cells, thereby preventing T1D development in both T1D models. These findings reveal a crucial cooperation between iNKT cells, pDCs, and T reg cells for prevention of T1D by viral infection.
Citation:
J Exp Med. 2011 Apr 11; 208(4):729-745
Issue Date:
11-Apr-2011
URI:
http://hdl.handle.net/10675.2/664
DOI:
10.1084/jem.20101692
PubMed ID:
21444661
PubMed Central ID:
PMC3135349
Type:
Article
ISSN:
1540-9538
Appears in Collections:
Immunotherapy Center Faculty: Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorDiana, Julienen_US
dc.contributor.authorBrezar, Vedranen_US
dc.contributor.authorBeaudoin, Lucieen_US
dc.contributor.authorDalod, Marcen_US
dc.contributor.authorMellor, Andrew L.en_US
dc.contributor.authorTafuri, Annaen_US
dc.contributor.authorvon Herrath, Matthiasen_US
dc.contributor.authorBoitard, Christianen_US
dc.contributor.authorMallone, Robertoen_US
dc.contributor.authorLehuen, Agnesen_US
dc.date.accessioned2012-10-26T16:27:01Z-
dc.date.available2012-10-26T16:27:01Z-
dc.date.issued2011-04-11en_US
dc.identifier.citationJ Exp Med. 2011 Apr 11; 208(4):729-745en_US
dc.identifier.issn1540-9538en_US
dc.identifier.pmid21444661en_US
dc.identifier.doi10.1084/jem.20101692en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/664-
dc.description.abstractType 1 diabetes (T1D) is an autoimmune disease resulting from T cellâ mediated destruction of insulin-producing β cells, and viral infections can prevent the onset of disease. Invariant natural killer T cells (iNKT cells) exert a regulatory role in T1D by inhibiting autoimmune T cell responses. As iNKT cellâ plasmacytoid dendritic cell (pDC) cooperation controls viral replication in the pancreatic islets, we investigated whether this cellular cross talk could interfere with T1D development during viral infection. Using both virus-induced and spontaneous mouse models of T1D, we show that upon viral infection, iNKT cells induce TGF-βâ producing pDCs in the pancreatic lymph nodes (LNs). These tolerogenic pDCs convert naive anti-islet T cells into Foxp3+ CD4+ regulatory T cells (T reg cells) in pancreatic LNs. T reg cells are then recruited into the pancreatic islets where they produce TGF-β, which dampens the activity of viral- and islet-specific CD8+ T cells, thereby preventing T1D development in both T1D models. These findings reveal a crucial cooperation between iNKT cells, pDCs, and T reg cells for prevention of T1D by viral infection.en_US
dc.rights© 2011 Diana et al.en_US
dc.titleViral infection prevents diabetes by inducing regulatory T cells through NKT cellâ plasmacytoid dendritic cell interplayen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3135349en_US
dc.contributor.corporatenameImmunotherapy Center-

Related articles on PubMed

All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.