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Inhibition of effector antigen-specific T cells by intradermal administration of heme oxygenase-1 inducers.
Simon, Thomas; Pogu, Julien; Rémy, Séverine; Brau, Frédéric; Pogu, Sylvie; Maquigneau, Maud; Fonteneau, Jean-François; Poirier, Nicolas; Vanhove, Bernard; Blancho, Gilles; Piaggio, Eliane; Anegon, Ignacio; Blancou, Philippe.
Afiliação
  • Simon T; Université de Nantes, Inserm, UMR1064, Center for Research in Transplantation and Immunology, 44093, Nantes, France; INRA USC1383, IECM; LUNAM Université, Oniris, Nantes, EA4644, France; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, US
  • Pogu J; Université de Nantes, Inserm, UMR1064, Center for Research in Transplantation and Immunology, 44093, Nantes, France.
  • Rémy S; Université de Nantes, Inserm, UMR1064, Center for Research in Transplantation and Immunology, 44093, Nantes, France.
  • Brau F; Université Côte d'Azur, Inserm, CNRS, IPMC, 06560, Valbonne, France.
  • Pogu S; INRA USC1383, IECM; LUNAM Université, Oniris, Nantes, EA4644, France.
  • Maquigneau M; Université de Nantes, Inserm, UMR1064, Center for Research in Transplantation and Immunology, 44093, Nantes, France.
  • Fonteneau JF; Université de Nantes, Inserm, UMR892, CNRS UMR6299, 44007, Nantes, France.
  • Poirier N; Université de Nantes, Inserm, UMR1064, Center for Research in Transplantation and Immunology, 44093, Nantes, France; OSE Immunotherapeutics, 44200 Nantes, France.
  • Vanhove B; Université de Nantes, Inserm, UMR1064, Center for Research in Transplantation and Immunology, 44093, Nantes, France.
  • Blancho G; Université de Nantes, Inserm, UMR1064, Center for Research in Transplantation and Immunology, 44093, Nantes, France.
  • Piaggio E; Institut Curie, Inserm, UMR932, 75005, Paris, France.
  • Anegon I; Université de Nantes, Inserm, UMR1064, Center for Research in Transplantation and Immunology, 44093, Nantes, France.
  • Blancou P; Université de Nantes, Inserm, UMR1064, Center for Research in Transplantation and Immunology, 44093, Nantes, France; Université Côte d'Azur, Inserm, CNRS, IPMC, 06560, Valbonne, France; INRA USC1383, IECM; LUNAM Université, Oniris, Nantes, EA4644, France. Electronic address: blancou@ipmc.cnrs.fr.
J Autoimmun ; 81: 44-55, 2017 Jul.
Article em En | MEDLINE | ID: mdl-28342735
ABSTRACT
Developing protocols aimed at inhibiting effector T cells would be key for the treatment of T cell-dependent autoimmune diseases including type 1 autoimmune diabetes (T1D) and multiple sclerosis (MS). While heme oxygenase-1 (HO-1) inducers are clinically approved drugs for non-immune-related diseases, they do have immunosuppressive properties when administered systemically in rodents. Here we show that HO-1 inducers inhibit antigen-specific effector T cells when injected intradermally together with the T cell cognate antigens in mice. This phenomenon was observed in both a CD8+ T cell-mediated model of T1D and in a CD4+ T cell-dependent MS model. Intradermal injection of HO-1 inducers induced the recruitment of HO-1+ monocyte-derived dendritic cell (MoDCs) exclusively to the lymph nodes (LN) draining the site of intradermal injection. After encountering HO-1+MoDCs, effector T-cells exhibited a lower velocity and a reduced ability to migrate towards chemokine gradients resulting in impaired accumulation to the inflamed organ. Intradermal co-injection of a clinically approved HO-1 inducer and a specific antigen to non-human primates also induced HO-1+ MoDCs to accumulate in dermal draining LN and to suppress delayed-type hypersensitivity. Therefore, in both mice and non-human primates, HO-1 inducers delivered locally inhibited effector T-cells in an antigen-specific manner, paving the way for repositioning these drugs for the treatment of immune-mediated diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T / Especificidade do Receptor de Antígeno de Linfócitos T / Heme Oxigenase-1 / Antígenos Tipo de estudo: Guideline Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T / Especificidade do Receptor de Antígeno de Linfócitos T / Heme Oxigenase-1 / Antígenos Tipo de estudo: Guideline Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article