1. Carbon monoxide-treated dendritic cells decrease β1-integrin induction on CD8 + T cells and protect from type 1 diabetes
- Author
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Simon, Thomas, Pogu, Sylvie, Tardif, Virginie, Rigaud, Kevin, Rémy, Severine, Piaggio, Eliane, Bach, Jean-Marie, Anegon, Ignacio, Blancou, Philippe, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Genetic and Cellular Engineering in Immunology and Regenerative Medicine (Team 2 - U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Immunologie - Immunopathologie - Immunothérapie (I3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fondation Centaure, Fondation Progreffe. Grant Number: 5–2010‐640., Région Pays de la Loire through the core facility Research and Development for Clinical Transfer., Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Le Bihan, Sylvie, Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Integrin beta1 ,Autoreactive CD8+ T cells ,Diabetes ,Down-Regulation ,β1-integrin ,Mice, Transgenic ,CD8-Positive T-Lymphocytes ,Autoantigens ,Dendritic cells ,Coculture Techniques ,Peptide Fragments ,Disease Models, Animal ,Mice ,Diabetes Mellitus, Type 1 ,Cell Movement ,Insulin-Secreting Cells ,Immune Tolerance ,Animals ,Humans ,Carbon monoxide ,Pancreas ,Cells, Cultured ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Carbon monoxide (CO) treatment improves pathogenic outcome of autoimmune diseases by promoting tolerance. However, the mechanism behind this protective tolerance is not yet defined. Here, we show in a transgenic mouse model for autoimmune diabetes that ex vivo gaseous CO (gCO)-treated DCs loaded with pancreatic β-cell peptides protect mice from disease. This protection is peptide-restricted, independent of IL-10 secretion by DCs and of CD4 + T cells. Although no differences were observed in autoreactive CD8 + T-cell function from gCO-treated versus untreated DC-immunized groups, gCO-treated DCs strongly inhibited accumulation of autoreactive CD8 + T cells in the pancreas. Interestingly , induction of β1-integrin was curtailed when CD8 + T cells were primed with gCO-treated DCs, and the capacity of these CD8 + T cells to lyse isolated islet was dramatically impaired. Thus, immunotherapy using CO-treated DCs appears to be an original strategy to control autoimmune disease.
- Published
- 2013
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