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Caractérisation De La Polarisation Des Macrophages Pulmonaires Humains Et Voies De Régulation Charlotte Abrial

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Caractérisation De La Polarisation Des Macrophages Pulmonaires Humains Et Voies De Régulation Charlotte Abrial Caractérisation de la polarisation des macrophages pulmonaires humains et voies de régulation Charlotte Abrial To cite this version: Charlotte Abrial. Caractérisation de la polarisation des macrophages pulmonaires humains et voies de régulation. Biologie cellulaire. Université de Versailles-Saint Quentin en Yvelines, 2014. Français. NNT : 2014VERS0033. tel-01326578 HAL Id: tel-01326578 https://tel.archives-ouvertes.fr/tel-01326578 Submitted on 8 Dec 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Université de Versailles Saint Quentin en Yvelines UFR DES SCIENCES DE LA SANTÉ École doctorale GAO "Des génomes aux organismes" Année universitaire 2014 – 2015 N° le 03 novembre 2014 THESE DE DOCTORAT Présentée pour l’obtention du grade de DOCTEUR DE L’UNIVERSITÉ VERSAILLES – SAINT QUENTIN EN YVELINES Spécialité : Biologie cellulaire Par Charlotte ABRIAL Caractérisation de la polarisation des macrophages pulmonaires humains et voies de régulation Composition du jury: Directeur de thèse Pr. DEVILLIER Philippe Rapporteur Dr. FROSSARD Nelly Rapporteur Pr. LAGENTE Vincent Examinateur Dr. TOUQUI Lhousseine Université de Versailles Saint Quentin en Yvelines UFR DES SCIENCES DE LA SANTÉ École doctorale GAO "Des génomes aux organismes" Année universitaire 2014 – 2015 N° THESE DE DOCTORAT Présentée pour l’obtention du grade de DOCTEUR DE L’UNIVERSITÉ VERSAILLES – SAINT QUENTIN EN YVELINES Spécialité : Biologie cellulaire Par Charlotte ABRIAL Caractérisation de la polarisation des macrophages pulmonaires humains et voies de régulation Composition du jury: Directeur de thèse Pr. DEVILLIER Philippe Rapporteur Dr. FROSSARD Nelly Rapporteur Pr. LAGENTE Vincent Examinateur Dr. TOUQUI Lhousseine "A journey of a thousand miles, begins with a single step..." Lao-tzu Pour toi, papa Remerciement C'est au terme d'un voyage de 4 ans que je souhaite remercier toutes les personnes qui ont partagé avec moi cette aventure. Je tiens tout d'abord à adresser mes remerciements aux membres du jury, Au Professeur Vincent Lagente, qui me fait l'honneur d'être rapporteur de cette thèse. Vous avez suivi mon parcours depuis mon master et toujours soutenue dans mes démarches. Grâce à vous j'ai pu connaitre le laboratoire du Professeur Devillier, ce qui m'a conduit jusque là. Je vous adresse mes sincères remerciements. Au Docteur Nelly Frossard, qui me fait l'honneur d'évaluer ma thèse en tant que rapporteur. Je vous remercie de l'attention et de la considération que vous avez porté à mon travail au cours de ces 3 ans et pour les remarques constructives que vous avez porté à mon égard lors de nos différents échanges en congrès. Je vous adresse mes sincères remerciements. Au Docteur Lhousseine Touqui, qui me fait l'honneur d'examiner mon travail de thèse. Je vous remercie de l'intérêt que vous avez porté à mon travail ainsi que d'avoir accepté de transmettre ma candidature à l'institut Pasteur. Je vous adresse mes sincères remerciements. Au Professeur Philippe Devillier, qui me fait l'honneur en tant que directeur de thèse d'être membre de mon jury. C’est avec émotion que je vous adresse mes plus sincères remerciements pour m'avoir acceptée chaleureusement au sein de votre laboratoire en stage de master et pour m'avoir offert l'opportunité de continuer jusqu'en thèse. Merci pour la confiance, l'encadrement et la compréhension dont vous avez fait preuve à mon égard et pour les nombreuses opportunités que j'ai eu de présenter mes travaux. Je vous adresse ma sincère reconnaissance et mon profond respect. Remerciement Ce travail, n'aurait pu aboutir sans le soutien des membres du laboratoire UPRES EA220. Je tiens à remercier chaleureusement, Le Docteur Stanislas Grassin-Delyle pour m'avoir encadrée dès mon arrivée au laboratoire et dont l'aboutissement de ce travail n'aurait pu se faire sans son aide, sa disponibilité et ses conseils bienveillants à mon égard. Merci pour tes encouragements et ta positivité à l'égard de mon travail. Le Docteur Emanuel Naline pour avoir fait en sorte que je ne manque de rien au laboratoire. Merci pour votre bonne humeur sans failles, vos découvertes culinaires et pour tout ces moments de belle rigolade passés en congrès et dont je garderai un très bon souvenir. Le Docteur Amparo Buenestado, pour m'avoir montrée et formée aux différentes techniques. Merci Amparotita, pour ton accueil chaleureux, tes conseils avisés et ta bonne humeur espagnole. Je me souviendrai toujours de mon premier congrès P2T avec toi ! En espérant te revoir très bientôt à Barcelone. La petite marlotte/charion pour avoir été et être toujours là quand il faut dans les bons comme les mauvais moments. J'ai toujours pu compter sur toi et à de nombreuses reprises. Ton soutien sans failles m'a été plus que nécessaire pour mener ce travail jusqu'au bout. Plus qu'une collègue tu es devenue au fil de ce voyage une véritable amie sur qui je peux compter. Je te souhaite avec Vincent plein de bonheur dans le futur. J'espère conserver ce lien d'amitié avec vous. Hélène et Tatiana qui m'ont généreusement aidée cette dernière année pour finaliser à bien ce travail. Un grand merci à vous les filles pour tout ce que vous avez fait pour moi afin que je puisse me concentrer sur la rédaction de ma thèse. A Hélène, à qui je souhaite plein de bonheur avec sa petite famille et de réussite dans son futur poste de chef de clinique à l'Hôpital Foch. En plus d'être un bon médecin tu feras une très bonne chercheuse! A Tatiana à qui je souhaite une réussite professionnelle et personnelle, avec Nico, à Rio de Janeiro, j'espère que l'on gardera contact malgré les nombreux kilomètres ! Remerciement Sonia pour son aide précieuse au cytomètre de flux et pour le temps que tu m’as accordé avec FlowJo ! Je te souhaite plein de courage pour l’année prochaine et une belle réussite professionnelle. Je remercie également les stagiaires Silvia, Sirima, Diane et Anthony pour leur collaboration à ce travail et auprès desquels j'ai appris à encadrer et déléguer. Une tâche pas toujours facile à accomplir. J'espère leur avoir transmis le goût de la recherche. Enfin, je souhaite remercier toute ma famille qui, au cours de ce voyage, ont été mes repères, mes 4 points cardinaux. A toi Maman pour m'avoir donnée la persévérance et avoir toujours cru en moi. A toi Noémie pour tous tes précieux conseils et pour me faire l'honneur d'être une seconde fois Tata. A toi Marie sur qui j'ai pu compter, à ma nièce Célie pour avoir égayé mon écran d'ordinateur et à mon beau frère David pour m'avoir encouragée. A toi mon petit loulou, pour avoir pris soin des gens que j'aime et être là quand je ne pouvais pas. Merci à ma belle famille, Martine, Yvon et Katell pour leur générosité et leur bienveillance à mon égard. Enfin ce voyage n'aurait pu aboutir sans toi matelot ! Tu as été la voile qui m'a permis d'avancer. Merci de m'avoir guidée et épaulée au travers des vagues. Merci pour ton soutien durant ce voyage et désolé pour mon retard. A deux dans le même bateau, ce n’était pas gagné, mais nous y sommes quand même arrivés... A jeter l'ancre ! Table des matières PREFACE ........................................................................................................ 1 INTRODUCTION ............................................................................................ 4 I. LES MACROPHAGES, CELLULES CLES DE L’INFLAMMATION ........................................ 5 A. Définition et origine ................................................................................................... 5 B. Les macrophages pulmonaires ................................................................................... 7 II. LA POLARISATION DES MACROPHAGES ......................................................................... 9 A. L’origine du concept de la polarisation ...................................................................... 9 B. Voie d’activation classique des macrophages en phénotype M1 ............................. 10 1) Les agonistes des Toll Like Receptors ................................................................. 10 2) Les cytokines de type Th1 .................................................................................... 12 a) L’interféron-γ ........................................................................................... 12 b) Le Tumor Necrosis Factor-α .................................................................... 15 C. Voie d’activation alternative des macrophages en phénotype M2 ........................... 15 1) Les macrophages réparateurs M2a ....................................................................... 16 a) Les cytokines de type Th2: l'Interleukine 4 et l'Interleukine 13 .............. 16 2) Les macrophages régulateurs M2b et M2c........................................................... 18 D. Propriétés fonctionnelles des macrophages et polarisation ...................................... 20 1) Production de médiateurs de l’inflammation ....................................................... 20 a) Les chimiokines .......................................................................................
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