University of Groningen. Gene-environment interactions in Inflammatory Bowel Disease Regeling, Anouk

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1 University of Groningen Gene-environment interactions in Inflammatory Bowel Disease Regeling, Anouk IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2014 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Regeling, A. (2014). Gene-environment interactions in Inflammatory Bowel Disease: Emphasis on smoking and autophagy ([S.l.] ed.) [S.n.] Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 Gene-environment interactions in Inflammatory Bowel Disease Emphasis on smoking and autophagy

3 The author gratefully acknowledges the financial support for printing this thesis by: Universitair Medisch Centrum Groningen Groninger University Institute for Drug Exploration Nederlandse Vereniging voor Gastroenterologie Sectie Experimentele Gastroenterologie (SEG) van de NVGE Rick Regeling - El Txoko taberna de pintxos Restaurant Louis XV en El Txoko te Groningen Cover design: Ridderprint BV, Ridderkerk, The Netherlands & Anouk Regeling Lay-out: Rianne Jongman (rianne_jongman@hotmail.com) Printed by: Ridderprint BV, Ridderkerk, The Netherlands ISBN (printed): ISBN (digital): , Anouk Regeling All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means without permission of the author.

4 Gene-environment interactions in Inflammatory Bowel Disease Emphasis on smoking and autophagy Proefschrift ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen op gezag van de rector magnificus prof. dr. E. Sterken en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op woensdag 8 oktober 2014 om uur door Anouk Regeling geboren op 27 juli 1981 te Hengelo

5 Promotores Prof. dr. K.N. Faber Prof. dr. G. Dijkstra Beoordelingscommissie Prof. dr. J.H. Kleibeuker Prof. dr. H.H. Kampinga Prof. dr. T.S. Stappenbeck

6 Voor mijn lieve pap en mam

7 Paranimfen Marije Boesjes Mariëtte van der Wulp

8 CONTENTS Chapter 1 General introduction 9 Chapter 2 Role of defective autophagia and the intestinal flora in 31 Crohn disease Self Nonself Oct;1(4): Chapter 3 Cigarette smoke enhances resistance to apoptosis; 47 relevance for its opposite effects in Inflammatory Bowel Diseases Submitted Chapter 4 HSPA6 is an ulcerative colitis susceptibility factor that is 71 induced by cigarette smoke and protects intestinal epithelial cells by stabilizing anti-apoptotic Bcl-XL Manuscript in preparation Chapter 5 Cigarette smoke has bacterium- and ATG16L1 allele- 107 specific effects on monocyte xenophagy promoting survival of pathogenic E. coli in Crohn s disease Submitted Chapter 6 The ATG16L1 T300A allele impairs clearance of 127 pathosymbionts in the inflamed ileal mucosa of Crohn s disease patients Gut, in press Chapter 7 Summarizing discussion and Future perspectives 151 Appendices Nederlandse samenvatting 173 Dankwoord/Acknowledgements 179 Biografie/Biography 187 List of publications 191

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