Abstract
(Macro)-autophagy is a homeostatic process by which eukaryotic cells dispose of protein aggregates and damaged organelles. Autophagy is also used to degrade micro-organisms that invade intracellularly in a process termed xenophagy. Genome-wide association scans have recently identified autophagy genes as conferring susceptibility to Crohn’s disease (CD), one of the chronic inflammatory bowel diseases, with evidence suggesting that CD arises from a defective innate immune response to enteric bacteria. Here we review the emerging role of autophagy in CD, with particular focus on xenophagy and enteric E. coli strains with an adherent and invasive phenotype that have been consistently isolated from CD patients with ileal disease.
Highlights
Introduction&URKQ¶V GLVHDVH &' RQH RI WKH PDMRU IRUPV RI LQIODPPDWRU\ ERZHO GLVHDVH ,%' LV D FKURQLF disease of the intestinal tract associated with significant morbidity [1]
Faculty of Life, Sport and Social Sciences, Edinburgh Napier University, Sighthill Campus, Edinburgh EH11 4BN, UK
16S rRNA sequence analysis revealed that patients with the NOD2 or autophagy-related 16-like 1 (ATG16L1) variants had significantly altered microbiota, the authors did acknowledge that the study was underpowered to determine any genera-specific effects
Summary
&URKQ¶V GLVHDVH &' RQH RI WKH PDMRU IRUPV RI LQIODPPDWRU\ ERZHO GLVHDVH ,%' LV D FKURQLF disease of the intestinal tract associated with significant morbidity [1]. Using 735 CD patients and 368 controls, single nucleotide polymorphisms (SNPs) with a p value < 0.01 were followed up in three independent cohorts This revealed a disease association with SNP rs2241880 in the autophagy-related 16-like 1 (ATG16L1) gene on chromosome 2q37.1. Resequencing of IRGM in 48 CD patients revealed three novel SNPs which were subsequently genotyped in an independent case-control cohort This demonstrated that only the silent 313T > C variant was associated with CD. Along with the original discovery of ATG16L1 variants, SNPs in the region of protein tyrosine phosphatase, non-receptor type 2 (PTPN2) were described [37] This was again replicated in several populations, including paediatric cohorts [58±60]. Genetic association studies have identified SNPs in unc-51-like kinase 1 (ULK1) [61,62], with conflicting results with regard to the association of variations in neutrophil cytosolic factor 4 (NCF4) [35,63,64]
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