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Caractérisation immunologique et protéomique des cellules dendritiques tolérogènes humaines. Application à la recherche de biomarqueurs de l’immunothérapie spécifique allergénique

Abstract : The aim of this thesis is to define biomarkers of allergen-specific immunotherapy (SIT).These biomarkers can be predictive of a clinical response or could be efficacy biomarkersable to discriminate responders versus non responder patients. The research strategy is based on the following hypothesis: if immunotherapy works, effector DCs are decreased where as regulatory DCs are increased locally or in the peripheral blood.First, we screened several biological or pharmacological agents to identify effector orregulatory DCs polarization agents. Four distinct molecules lead to the generation of eitherDC1, DC17 or regulatory DCs. In particular, proteases from Aspergillus Oryzae were clearinducer of tolerogenic DCs. The phenotype of those cells and the CD4+ T cell polarization induced after coculture were characterized extensively.In a second part, two proteomic approaches were used to compare the whole cell proteome of generated DCs. Most pertinent markers of polarization were validated in several cellular models. Markers were also followed in a randomized, double blind, placebo controlled clinical trial testing the efficacy of grass pollen tablets. Two markers were up regulated in patients who responded to the treatment pointing to a potential role of these proteins as early efficacy biomarkers. These markers are of crucial interest in the follow up of patients after SIT and could also be used in other diseases like autoimmune diseases or transplantation.
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https://tel.archives-ouvertes.fr/tel-00736730
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Submitted on : Saturday, September 29, 2012 - 1:01:34 AM
Last modification on : Tuesday, October 18, 2022 - 3:39:36 AM
Long-term archiving on: : Sunday, December 30, 2012 - 2:55:13 AM

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  • HAL Id : tel-00736730, version 1

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Aline Zimmer. Caractérisation immunologique et protéomique des cellules dendritiques tolérogènes humaines. Application à la recherche de biomarqueurs de l’immunothérapie spécifique allergénique. Sciences agricoles. Université Paris Sud - Paris XI, 2011. Français. ⟨NNT : 2011PA114818⟩. ⟨tel-00736730⟩

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