L’autophagie garante de l’immunité et de l’inflammation

Lapaquette, Pierre; Nguyen, Hang Thi Thu; Faure, Mathias

doi:10.1051/medsci/20173303018

Cited by 10 publications

(8 citation statements)

References 54 publications

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“…The pioneer evidence for the implication of autophagy in IBD etiology came from genome-wide association studies, which revealed single nucleotide polymorphisms (SNPs) in the autophagy-associated genes as susceptibility factors for CD. Most evidence for the association between these genetic variants and IBD etiology has come from functional studies using the ATG16L1 (autophagy related 16 like 1) T300A variant [2,5]. Pioneer studies showed that human cells having the ATG16L1 T300A variant exhibit impaired autophagy-mediated clearance of intracellular bacteria and increased pro-inflammatory cytokine production [5].…”

Section: Introductionmentioning

confidence: 99%

“…Most evidence for the association between these genetic variants and IBD etiology has come from functional studies using the ATG16L1 (autophagy related 16 like 1) T300A variant [2,5]. Pioneer studies showed that human cells having the ATG16L1 T300A variant exhibit impaired autophagy-mediated clearance of intracellular bacteria and increased pro-inflammatory cytokine production [5]. Paneth cells from CD patients homozygous for the ATG16L1 T300A allele, or from mice hypomorphic for Atg16l1 expression (Atg16l1[HM] mice), mice with Atg16l1 depletion specifically in intestinal epithelial cells (Atg16l1[ΔIEC] mice) or knock-in mice expressing the ATG16L1 T300A variant exhibit structural and functional aberrances with decreased expression of antimicrobial peptides [2,5].…”

Section: Introductionmentioning

confidence: 99%

“…Pioneer studies showed that human cells having the ATG16L1 T300A variant exhibit impaired autophagy-mediated clearance of intracellular bacteria and increased pro-inflammatory cytokine production [5]. Paneth cells from CD patients homozygous for the ATG16L1 T300A allele, or from mice hypomorphic for Atg16l1 expression (Atg16l1[HM] mice), mice with Atg16l1 depletion specifically in intestinal epithelial cells (Atg16l1[ΔIEC] mice) or knock-in mice expressing the ATG16L1 T300A variant exhibit structural and functional aberrances with decreased expression of antimicrobial peptides [2,5]. The ATG16L1 T300A variant also leads to defects in autophagy induction, bacterial trafficking and antigen processing and presentation in dendritic cells (DCs) [2,5].…”

Section: Introductionmentioning

confidence: 99%

“…Paneth cells from CD patients homozygous for the ATG16L1 T300A allele, or from mice hypomorphic for Atg16l1 expression (Atg16l1[HM] mice), mice with Atg16l1 depletion specifically in intestinal epithelial cells (Atg16l1[ΔIEC] mice) or knock-in mice expressing the ATG16L1 T300A variant exhibit structural and functional aberrances with decreased expression of antimicrobial peptides [2,5]. The ATG16L1 T300A variant also leads to defects in autophagy induction, bacterial trafficking and antigen processing and presentation in dendritic cells (DCs) [2,5]. Together, these studies suggest a role for ATG16L1 in the control of intestinal epithelial homeostasis and inflammatory immune responses.…”

Section: Introductionmentioning

confidence: 99%

“…The interaction between ATG16L1 and NOD2 (nucleotide-binding oligomerization domain containing 2), encoded by the first CD susceptibility gene, reinforces the importance of autophagy in CD pathogenesis. Indeed, the CD-associated NOD2 L1007fsinsC frameshift mutation leads to impaired autophagy-mediated intracellular bacterial clearance, due to a defect in recruiting ATG16L1 to the plasma membrane at the bacterial entry site, and fails to promote major histocompatibility complex (MHC) II-mediated antigen presentation by DCs [2,5]. Further studies have shown a link between the CD-associated susceptibility gene IRGM (immunity related GTPase M) and defect in autophagy-mediated clearance of CDassociated adherent-invasive Escherichia coli (AIEC), as well as the association between granulomas, one of the microscopic hallmarks of CD, and the genetic variants in the autophagyassociated genes ATG4A, ATG2A, FNBP1L (formin binding protein 1 like) and ATG4D [2,5].…”

Section: Introductionmentioning

confidence: 99%

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New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD

2019

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One of the most significant challenges of inflammatory bowel disease (IBD) research is to understand how alterations in the symbiotic relationship between the genetic composition of the host and the intestinal microbiota, under impact of specific environmental factors, lead to chronic intestinal inflammation. Genome-wide association studies, followed by functional studies, have identified a role for numerous autophagy genes in IBD, especially in Crohn disease. Studies using in vitro and in vivo models, in addition to human clinical studies have revealed that autophagy is pivotal for intestinal homeostasis maintenance, gut ecology regulation, appropriate intestinal immune responses and anti-microbial protection. This review describes the latest researches on the mechanisms by which dysfunctional autophagy leads to disrupted intestinal epithelial function, gut dysbiosis, defect in anti-microbial peptide secretion by Paneth cells, endoplasmic reticulum stress response and aberrant immune responses to pathogenic bacteria. A better understanding of the role of autophagy in IBD pathogenesis may provide better sub-classification of IBD phenotypes and novel approaches for disease management.

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Section: Introductionmentioning

confidence: 99%