title: Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay.
abstract: Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell-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 cell-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-β-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.
authors: Institut National de la Santé et de la Recherche Médicale Unité 986, Hôpital Cochin/St Vincent de Paul, 75674 Paris, Cedex 14, France.
authors: Julien
authors: J
authors: Diana
authors: Vedran
authors: V
authors: Brezar
authors: Lucie
authors: L
authors: Beaudoin
authors: Marc
authors: M
authors: Dalod
authors: Andrew
authors: A
authors: Mellor
authors: Anna
authors: A
authors: Tafuri
authors: Matthias
authors: M
authors: von Herrath
authors: Christian
authors: C
authors: Boitard
authors: Roberto
authors: R
authors: Mallone
authors: Agnès
authors: A
authors: Lehuen
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology; D060890:B7-H1 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002450:Cell Communication; D003713:Dendritic Cells / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D016753:Interleukin-10 / Q000502:physiology; D007515:Islets of Langerhans / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D055611:Natural Killer T-Cells / Q000502:physiology*; D010455:Peptides / Q000502:physiology; D061026:Programmed Cell Death 1 Receptor; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D016212:Transforming Growth Factor beta; D016753:Interleukin-10