Étude prospective pilote des effets d'une exposition ex vivo de lymphocytes T humains à la pollution atmosphérique particulaire : recherche de biomarqueurs et influence de l'âge

Abstract : Atmospheric fine particulate matter (FP) are able to enter the lungs where some compounds can interact with lung cells and reach the bloodstream . Exposure to FP affects in particular susceptible populations such as the elderly. This thesis is part of a project aiming to identify the effects of FP on human T lymphocytes (LT) while attempting to determine biomarkers related to exposure and to evaluate the variation of the cellular response as a function of age. LT were isolated from blood samples of 91 volunteers belonging to three age groups (20-30, 45-55, 70-85 years) then exposed ex vivo for 72h to 45 µg/µl of FP collected in Dunkirk. The steps of isolation, purification and activation of LT were first optimized. Following the characterization of the sampled population, a homogeneous study population was selected (10 subjects/age class). We have demonstrated an induction of the genes coding for the enzymes involved in the metabolic activation of PAH identified in the PF sample. Characterization of the LT profile made it possible to propose a mixed th1/th2 profile cause by the exposure. Teh transcriptomic study of miRNAs revealed an overexpression of miR-124-3p involved in the regulation of several functions in the immune system and miR-1290 involved in several types of cancer. As for the influence of age, overexpression of the genes coding for the antioxidant enzymes (NQO1 and HMOX1), an increase in the concentration of cytokines (IL-4 and IL-13) as well as a modification of the expression profile of some miRNAs were noted on the elderly.
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Margueritta Al Zallouha. Étude prospective pilote des effets d'une exposition ex vivo de lymphocytes T humains à la pollution atmosphérique particulaire : recherche de biomarqueurs et influence de l'âge. Toxicologie. Université du Littoral Côte d'Opale, 2017. Français. ⟨NNT : 2017DUNK0472⟩. ⟨tel-02145214⟩

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