Implication des lymphocytes B et de BAFF dans l'apoptose des cellules épithéliales des glandes salivaires au cours du syndrome de Gougerot-Sjögren

Abstract : Sjögren’s syndrome (SS) is an inflammatory systemic autoimmune disease (AID), mainly characterized by the decrease of salivary and lachrymal secretions. This leads to dry mouthand dry eyes. This chronic disease principally affects women around menopause. At the physiological level, salivary gland (SG) epithelial tissue is infiltrated by lymphocytes, leading to epithelial cells (EC) apoptosis. As epigenetics can play an important role in AID- such asSS development, we investigated human endogenous retroviral elements (HERV) and microRNA expression. Furthermore, in order to better understand the cellular and molecular mechanisms implied in lymphocyte-EC interactions in pathological SG, we set up an in vitroco-culture model between EC and B and T cells. We also studied BAFF role on EC which express one of its receptors, BR3. First, we demonstrated that in SS SG, HERVs and miRNAs show a distinct profile from healthy controls, indicating that epigenetics is implied in the pathology. Secondly, we showed that EC undergo apoptosis following direct interaction with T and B cells, via two distincts ignaling pathways: Fas pathway for T cells and PKCδ pathway for B cells. Linked with Bcell-induced apoptosis, we demonstrated that BAFF is implied in EC survival, and that BAFFsignaling blocking or BR3 down-regulation leads to EC death. We may suppose that B cells compete with EC for survival signaling from BAFF, and that EC die from lack of it. Finally, we showed that several forms of BAFF are expressed by EC and that they are differentially recognized by anti-BAFF antibodies. These may be more or less glycozylated BAFF isoformsor BAFF variants. Further studies are needed to identify them.
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Human health and pathology. Université de Bretagne occidentale - Brest, 2012. French. <NNT : 2012BRES0001>


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Marie-Michèle Varin. Implication des lymphocytes B et de BAFF dans l'apoptose des cellules épithéliales des glandes salivaires au cours du syndrome de Gougerot-Sjögren. Human health and pathology. Université de Bretagne occidentale - Brest, 2012. French. <NNT : 2012BRES0001>. <tel-00713910>

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