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Mécanisme d'action du phosphopeptide P140 dans la modulation de la réponse autoimmune du lupus

Abstract : Systemic lupus erythematosus is a multi-organ autoimmune disease provoking tissue damages. Our laboratory has discovered a phosphorylated peptide, named P140, with therapeutic activities in lupus. The mode of action used by P140 peptide relies on its interaction with the heat shock protein HSPA8/HSC70. The aim of my thesis project was to consolidate and complete this HSPA8-dependent mechanism. We have demonstrated that, upon internalization by clathrin-mediated endocytosis, P140 peptide homes rapidly into B cell lysosome. In this organelle, the peptide reduces chaperone-mediated autophagy by interacting and inhibiting intralysosomal HSPA8 activity. We also performed a comparative analysis of T cell and B cell repertoire on lupic mice compared to healthy mice Our results show a modification in the frequency of certain TCR rearrangements between lupus-prone mice and healthy mice and a beneficial effect of P140 peptide on certain lupus-associated rearrangements.
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https://tel.archives-ouvertes.fr/tel-02003601
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Submitted on : Friday, February 1, 2019 - 12:23:01 PM
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Christophe Macri. Mécanisme d'action du phosphopeptide P140 dans la modulation de la réponse autoimmune du lupus. Immunologie. Université de Strasbourg, 2013. Français. ⟨NNT : 2013STRAJ074⟩. ⟨tel-02003601⟩

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