Marine Besnard, France

Center of Research in Transplantation and Immunology, CRTI - UMR1064 Center of Research in Transplantation and Immunology, CRTI - UMR1064
Graduated with a Bachelor's degree in 2016 and then a Master's degree in 2018 from the University of Nantes (France) in Biotechnology and Therapeutic Research. I started working on tolerance mechanisms and AIRE in 2017 at the Research Center in Transplantation and Immunology (CRTI UMR1064) in Nantes. I am currently finishing my thesis, started in 2018, on the evaluation of the potential of anti-CD45RC immunotherapy for the treatment of the APECED syndrome.

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ANTI-CD45RC MAB IMMUNOTHERAPY CONTROLS THE DEVELOPMENT OF AUTO-IMMUNE SYMPTOMS IN AN APECED RAT MODEL OF AIRE DEFICIENCY

Session Name
PS53 - IMMUNE DEFICIENCY AND AUTOIMMUNITY
Session Type
PARALLEL SESSIONS
Date
31.05.2021, Monday
Session Time
13:30 - 15:30
Room
HALL G
Lecture Time
14:40 - 14:50
Presenter
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Abstract

Background and Aims

Auto-immune regulator (AIRE) is a key transcription regulator that allows negative selection by promoting the expression of tissue restricted antigens in the thymus. In human, AIRE-deficiency results in the development of autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED), a lethal autoimmune disease characterized by lesions of multiple peripheral organs and production of many autoantibodies. To date, no cure is available.

Methods

Recently, our team generated the first Aire-/- rat model. In contrast to mouse models, these animals harbor several key features of APECED and are therefore a pertinent model for preclinical studies. We previously showed that targeting CD45RC enables a selective depletion of effector T cells (Teffs) while preserving and boosting regulatory T cells (Tregs). Moreover, anti-CD45RC mAb therapy was protective in transplantation. To address the potential of anti-CD45RC immunotherapy to control APECED autoimmune symptoms, we tested this treatment in our model.

Results

First, we demonstrated that anti-CD45RC mAbs efficiently reduced alopecia and vitiligo presented by Aire-/- animals. Besides, isotype-treated Aire-/- rats showed complete destruction of exocrine pancreas and loss of thymus structure whereas these organs were preserved by anti-CD45RC mAbs therapy. Interestingly, this treatment also decreased the production of autoantibodies and modified Tregs’ transcriptome. Finally, analysis of PBMCs from APECED patients confirmed that the expression of CD45RC was similar to the one observed in Aire-/- rats.

Conclusions

In conclusion, we demonstrated that anti-CD45RC immunotherapy was able to control the development of auto-immune symptoms in Aire-/- rats. Furthermore, CD45RC expression was conserved between our model and APECED patients underlying the clinical potential of CD45RC targeting in this disease.

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