📇 Rhumatologue · MONTFERMEIL · (93) · Salarié

MME MARINE BESNARD

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Praticien-chercheur
9 articles scientifiques publiés — formation continue solide
Disponibilité géographique
2 lieux d'exercice — choisissez celui qui vous arrange
Délais de RDV courts dans la région
78.3 rhumatos / 100 000 hab. — département bien doté

Rhumatologue

📍 MONTFERMEIL (93)SalariéRPPS 10101089935

Publications actives

5ans d'exercice (thèse 2021)·6 publications sur 5 ans

📊 Reconnaissance scientifique : 5/100📝 11 articles publiés🇫🇷 Publications académiques françaises (8)

✨ Génération du profil synthétique IA en cours…

Données ANS publiques (Licence Ouverte 2.0) · Enrichissements MonRhumato 100 % opt-in · Toute personne référencée peut demander la suppression ou la rectification.

Top publications · les plus citées

The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1

The New England journal of medicine · 2024

📚 67 citations🎯 RCR 11.27Top 2% NIH🩺 Clinique🔓 Open Access📄 PDF gratuit ↗

Breakdown of Immune Tolerance in AIRE-Deficient Rats Induces a Severe Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy-like Autoimmune Disease

Journal of immunology (Baltimore, Md. : 1950) · 2018

📚 28 citations🎯 RCR 1.03

Lire l'abstract Crossref ↓

Abstract Autoimmune regulator (AIRE) deficiency in humans induces a life-threatening generalized autoimmune disease called autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), and no curative treatments are available. Several models of AIRE-deficient mice have been generated, and although they have been useful in understanding the role of AIRE in central tolerance, they do not reproduce accurately the APECED symptoms, and thus there is still a need for an animal model displaying APECED-like disease. We assessed, in this study, the potential of the rat as an accurate model for APECED. In this study, we demonstrate that in rat, AIRE is expressed by MHC class II (MCH-II)+ and MHC-II− medullary thymic epithelial cells in thymus and by CD4int conventional dendritic cells in periphery. To our knowledge, we generated the first AIRE-deficient rat model using zinc-finger nucleases and demonstrated that they display several of the key symptoms of APECED disease, including alopecia, skin depigmentation, and nail dystrophy, independently of the genetic background. We observed severe autoimmune lesions in a large spectrum of organs, in particular in the pancreas, and identified several autoantibodies in organs and cytokines such as type I IFNs and IL-17 at levels similar to APECED. Finally, we demonstrated a biased Ab response to IgG1, IgM, and IgA isotypes. Altogether, our data demonstrate that AIRE-deficient rat is a relevant APECED animal model, opening new opportunity to test curative therapeutic treatments.

AIRE deficiency, from preclinical models to human APECED disease

Disease models & mechanisms · 2021

📚 24 citations🎯 RCR 1.54🔓 Open Access📄 PDF gratuit ↗

Lire l'abstract Crossref ↓

ABSTRACT Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare life-threatening autoimmune disease that attacks multiple organs and has its onset in childhood. It is an inherited condition caused by a variety of mutations in the autoimmune regulator (AIRE) gene that encodes a protein whose function has been uncovered by the generation and study of Aire-KO mice. These provided invaluable insights into the link between AIRE expression in medullary thymic epithelial cells (mTECs), and the broad spectrum of self-antigens that these cells express and present to the developing thymocytes. However, these murine models poorly recapitulate all phenotypic aspects of human APECED. Unlike Aire-KO mice, the recently generated Aire-KO rat model presents visual features, organ lymphocytic infiltrations and production of autoantibodies that resemble those observed in APECED patients, making the rat model a main research asset. In addition, ex vivo models of AIRE-dependent self-antigen expression in primary mTECs have been successfully set up. Thymus organoids based on pluripotent stem cell-derived TECs from APECED patients are also emerging, and constitute a promising tool to engineer AIRE-corrected mTECs and restore the generation of regulatory T cells. Eventually, these new models will undoubtedly lead to main advances in the identification and assessment of specific and efficient new therapeutic strategies aiming to restore immunological tolerance in APECED patients.

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MME MARINE BESNARD

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Thèses universitaires

Activité de recherche & publications

Publications académiques en France

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Top publications · les plus citées

Publications scientifiques (9) — classées par pathologie

Transversal7

SAPL1

Tendinopathies & SCC1

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