Frontiers in Immunology (Sep 2019)
Immunophenotype of a Rat Model of Duchenne's Disease and Demonstration of Improved Muscle Strength After Anti-CD45RC Antibody Treatment
- Laure-Hélène Ouisse,
- Laure-Hélène Ouisse,
- Laure-Hélène Ouisse,
- Séverine Remy,
- Séverine Remy,
- Séverine Remy,
- Aude Lafoux,
- Thibaut Larcher,
- Laurent Tesson,
- Laurent Tesson,
- Laurent Tesson,
- Vanessa Chenouard,
- Vanessa Chenouard,
- Vanessa Chenouard,
- Carole Guillonneau,
- Carole Guillonneau,
- Lucas Brusselle,
- Lucas Brusselle,
- Lucas Brusselle,
- Nadège Vimond,
- Nadège Vimond,
- Karl Rouger,
- Yann Péréon,
- Alexis Chenouard,
- Christèle Gras-Le Guen,
- Cécile Braudeau,
- Cécile Braudeau,
- Cécile Braudeau,
- Régis Josien,
- Régis Josien,
- Régis Josien,
- Corinne Huchet,
- Corinne Huchet,
- Ignacio Anegon,
- Ignacio Anegon,
- Ignacio Anegon
Affiliations
- Laure-Hélène Ouisse
- Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France
- Laure-Hélène Ouisse
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
- Laure-Hélène Ouisse
- Transgenesis Rat ImmunoPhenomic Facility, CRTI UMR 1064, Nantes, France
- Séverine Remy
- Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France
- Séverine Remy
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
- Séverine Remy
- Transgenesis Rat ImmunoPhenomic Facility, CRTI UMR 1064, Nantes, France
- Aude Lafoux
- THERASSAY CAPACITES, Université de Nantes, Nantes, France
- Thibaut Larcher
- INRA, UMR703 APEX, Oniris, Ecole Nationale Vétérinaire, Agro-alimentaire et de l'alimentation, Nantes, France
- Laurent Tesson
- Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France
- Laurent Tesson
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
- Laurent Tesson
- Transgenesis Rat ImmunoPhenomic Facility, CRTI UMR 1064, Nantes, France
- Vanessa Chenouard
- Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France
- Vanessa Chenouard
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
- Vanessa Chenouard
- Transgenesis Rat ImmunoPhenomic Facility, CRTI UMR 1064, Nantes, France
- Carole Guillonneau
- Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France
- Carole Guillonneau
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
- Lucas Brusselle
- Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France
- Lucas Brusselle
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
- Lucas Brusselle
- Transgenesis Rat ImmunoPhenomic Facility, CRTI UMR 1064, Nantes, France
- Nadège Vimond
- Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France
- Nadège Vimond
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
- Karl Rouger
- INRA, UMR703 APEX, Oniris, Ecole Nationale Vétérinaire, Agro-alimentaire et de l'alimentation, Nantes, France
- Yann Péréon
- Reference Centre for Neuromuscular Diseases AOC, CHU Nantes, Nantes, France
- Alexis Chenouard
- Pediatric Intensive Care, Hôpital Mère Enfant, CHU Nantes, Nantes, France
- Christèle Gras-Le Guen
- Clinical Investigation Center 1413 INSERM 1043, CHU Nantes, Nantes, France
- Cécile Braudeau
- Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France
- Cécile Braudeau
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
- Cécile Braudeau
- CIMNA, Laboratoire d'Immunologie, CHU Nantes, Nantes, France
- Régis Josien
- Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France
- Régis Josien
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
- Régis Josien
- CIMNA, Laboratoire d'Immunologie, CHU Nantes, Nantes, France
- Corinne Huchet
- THERASSAY CAPACITES, Université de Nantes, Nantes, France
- Corinne Huchet
- 0Thérapie Génique Translationnelle des Maladies Génétiques, INSERM UMR 1089, Nantes, France
- Ignacio Anegon
- Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France
- Ignacio Anegon
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
- Ignacio Anegon
- Transgenesis Rat ImmunoPhenomic Facility, CRTI UMR 1064, Nantes, France
- DOI
- https://doi.org/10.3389/fimmu.2019.02131
- Journal volume & issue
-
Vol. 10
Abstract
Corticosteroids (CS) are standard therapy for the treatment of Duchenne's muscular dystrophy (DMD). Even though they decrease inflammation, they have limited efficacy and are associated with significant side effects. There is therefore the need for new protolerogenic treatments to replace CS. Dystrophin-deficient rats (Dmdmdx) closely resemble the pathological phenotype of DMD patients. We performed the first Immunophenotyping of Dmdmdx rats and showed leukocyte infiltration in skeletal and cardiac muscles, which consisted mostly of macrophages and T cells including CD45RChigh T cells. Muscles of DMD patients also contain elevated CD45RChigh T cells. We treated Dmdmdx rats with an anti-CD45RC MAb used in previous studies to deplete CD45RChigh T cells and induce immune tolerance in models of organ transplantation. Treatment of young Dmdmdx rats with anti-CD45RC MAb corrected skeletal muscle strength and was associated with depletion of CD45RChigh T cells with no side effects. Treatment of young Dmdmdx rats with prednisolone resulted in increase in skeletal muscle strength but also severe growth retardation. In conclusion, anti-CD45RC MAb treatment has potential in the treatment of DMD and might eventually result in reduction or elimination of CS use.
Keywords