The T300A variant in ATG16L1 is one of the most well known CD-associated variants and a potential interaction with cigarette smoking was not yet identified.
ATG16L1 is essential for non-selective autophagy, a process important for cell survival, but it also plays a crucial role in confering resistance to infection by elimination intracellular pathogens, thereby defining mucosal tolerance. Here, we show that uptake of E. coli and of the pathogenic variant (AIEC) was increased in monocytes carrying the T300A variant and cigarette smoke only impaired the uptake of AIEC. Further, monocytes carrying the T300A variant showed impaired killing of AIEC, especially in combination with inflammatory triggers or cigarette smoke, resulting in modulation of intestinal flora, thereby further aggravating CD pathology.
|Translated title of the contribution||Interacties tussen genetische en omgevingsfactoren in inflammatoire darmziekten: Focus op roken en autofagie|
|Qualification||Doctor of Philosophy|
|Place of Publication||[S.l.]|
|Publication status||Published - 2014|
Bakker, S. (Creator), Dotinga, A. (Creator), Vonk, J. (Creator), Smidt, N. (Creator), Scholtens, S. (Creator), Swertz, M. (Creator), Wijmenga, C. (Creator), Wolffenbuttel, B. (Creator), Stolk, R. (Creator), van Zon, S. (Creator), Rosmalen, J. (Creator), Postma, D. S. (Creator), de Boer, R. (Creator), Navis, G. (Creator), Slaets, J. (Creator), Ormel, H. (Creator), van Dijk, F. (Creator) & Bolmer, B. (Data Manager), Lifelines, 2006