In Vivo Requirement for Atg5 in Antigen Presentation by Dendritic Cells

Lee, Kyung-Mi; Mattei, Lisa M.; Steinberg, Benjamin E.; Alberts, Pēteris; Lee, Yun Hee; Chervonsky, Alexander V.; Mizushima, Noboru; Grinstein, Sergio; Iwasaki, Akiko

doi:10.1016/j.immuni.2009.12.006

Cited by 436 publications

(470 citation statements)

References 62 publications

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“…Of note, double-membrane bound autophagosomes are not observed during this process and the authors hypothesise involvement of Atg5 in a non-canonical autophagy pathway. Together, this suggests that the Atg protein Atg5, but not canonical autophagy, is required for exogenous antigen processing and presentation by MHCII molecules (Lee et al, 2010).…”

Section: Autophagy In Mhc Class II Antigen Presentationmentioning

confidence: 96%

“…CD11c + cDC from Atg5-deficient foetal liver reconstituted mice infected with either ovalbumin-herpes simplex virus-2 (OVA-HSV-2) or OVA-Listeria monocytogenes, are unable to efficiently prime adoptively transferred OVA-specific CD4 + OT-II T cells and induce OT-II T cell proliferation in vivo (Lee et al, 2010). Furthermore, protective immune responses require Atg5 expression by cDC.…”

Section: Autophagy In Mhc Class II Antigen Presentationmentioning

confidence: 99%

“…Furthermore, protective immune responses require Atg5 expression by cDC. The authors rule out a role for Atg5 in surface expression of MHCII, CD40 and CD86, the production of inflammatory cytokines or DC migration (Lee et al, 2010). The absence of Atg5 does not affect lysosome function, instead Atg5-deficient cDC are unable to present antigen on MHCII molecules due to the reduced ability of phagosomes to fuse with lysosomes (Lee et al, 2010).…”

Section: Autophagy In Mhc Class II Antigen Presentationmentioning

confidence: 99%

“…The authors rule out a role for Atg5 in surface expression of MHCII, CD40 and CD86, the production of inflammatory cytokines or DC migration (Lee et al, 2010). The absence of Atg5 does not affect lysosome function, instead Atg5-deficient cDC are unable to present antigen on MHCII molecules due to the reduced ability of phagosomes to fuse with lysosomes (Lee et al, 2010). Of note, double-membrane bound autophagosomes are not observed during this process and the authors hypothesise involvement of Atg5 in a non-canonical autophagy pathway.…”

Section: Autophagy In Mhc Class II Antigen Presentationmentioning

confidence: 99%

“…Experiments by Lee et. al. suggest that autophagy does not affect MHCI cross-presentation in murine DC (Lee et al, 2010). To investigate cross-presentation, the ability of wildtype DC versus Atg5-deficient DC to cross-present either soluble OVA, or lethally irradiated OVA-pulsed MHCI-deficient splenocytes, to CD8 + OVA-specific OT-I T cells was examined.…”

Section: Mhci Cross-presentation and Autophagymentioning

confidence: 99%

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Intersection of autophagy with pathways of antigen presentation

Patterson

Mintern

2012

Protein Cell

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Traditionally, macroautophagy (autophagy) is viewed as a pathway of cell survival. Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of stress. Interestingly, autophagy can also directly intersect with, and impact, other major pathways of cellular function. Here, we will review the contribution of autophagy to pathways of antigen presentation. The autophagy machinery acts to modulate both MHCI and MHCII antigen presentation. As such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.

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Section: Autophagy In Mhc Class II Antigen Presentationmentioning

confidence: 96%

Section: Autophagy In Mhc Class II Antigen Presentationmentioning

confidence: 99%

Section: Autophagy In Mhc Class II Antigen Presentationmentioning

confidence: 99%

Section: Autophagy In Mhc Class II Antigen Presentationmentioning

confidence: 99%

Section: Mhci Cross-presentation and Autophagymentioning

confidence: 99%

See 3 more Smart Citations

Intersection of autophagy with pathways of antigen presentation

Patterson

Mintern

2012

Protein Cell

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A comparative proteomics study of a synovial cell line stimulated with TNF‐α

et al. 2016

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To elucidate the pathogenesis of rheumatoid arthritis (RA), we used proteomic analysis to determine the protein profile in a synovial cell line, MH7A, established from patients with RA. Proteins were extracted from MH7A cells that were or were not stimulated with tumor necrosis factor‐α (TNF‐α), and then analyzed on a liquid chromatography/mass spectrometry system equipped with a unique long monolithic silica capillary. On the basis of the results of this proteomic analysis, we identified 2650 proteins from untreated MH7A cells and 2688 proteins from MH7A cells stimulated with TNF‐α. Next, we selected 269 differentially produced proteins that were detected only under TNF‐α stimulation, and classified these proteins by performing gene ontology analysis by using DAVID as a functional annotation tool. In TNF‐α‐stimulated MH7A cells, we observed substantial production of plasminogen‐activator inhibitor 2 and apoptosis‐regulating proteins such as BH3‐interacting domain death agonist, autophagy protein 5, apolipoprotein E, and caspase‐3. These results indicate that the upregulation of plasminogen‐activator inhibitor 2 and apoptosis‐regulating proteins in synovial cells in response to TNF‐α stimulation might represent a predominant factor that contributes to the pathogenesis of RA.

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Role of Autophagy‐Related Genes in the Pathology of Inflammatory Bowel Disease

Tian

Kabi

McDonald

2013

Encyclopedia of Life Sciences

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Inflammatory bowel disease (IBD) is a complex, multifactorial disease with genetic, microbial and environmental risk factors combining to result in recurrent inflammation of the intestine. Genetic analyses have uncovered a cluster of IBD risk genes, which regulate a cell stress response called autophagy. Functional studies of these autophagy‐related genes highlight contributions of disease‐associated dysregulation to several aspects of IBD pathology, which include alterations in microbiome composition and bacterial responses (xenophagy), antimicrobial peptide production by Paneth cells (crinophagy), enhanced levels of proinflammatory cytokines and enhanced T‐cell subset responses. This suite of autophagy‐gene regulated responses is modulated not only by the cell type or stimulus, but also by environmental context, with the overall balance of responses critical to the maintenance of health or induction of disease. These findings have opened up new avenues for the development of IBD therapeutics and increased understanding of disease mechanisms to facilitate a more personalised approach to the treatment of IBD. Key Concepts: Susceptibility to IBD disease is associated with genetic variants in a spectrum of autophagy‐related genes. Autophagy is a tightly regulated catabolic degradative pathway implicated in a number of disease‐associated processes. Autophagy‐dependent processes altered in IBD include intracellular bacterial killing by xenophagy, Paneth cell antimicrobial peptide secretion via crinophagy, production of proinflammatory cytokines by macrophages, antigen presentation and endoplasmic reticulum (ER) stress responses in enterocytes. Xenophagy is impaired by IBD‐associated polymorphisms in ATG16L1 , IRGM , NOD2 , RIP2 , PTPN2 and XBP1 resulting in chronic inflammation due to defective clearance of intracellular pathogens. Both impaired and enhanced crinophagy are observed in Paneth cells from IBD patients. Alterations in crinophagy supress secretion of antimicrobial peptides by these cells. Proinflammatory cytokine production by macrophages is enhanced in IBD. This process is regulated by a balance between autophagy and inflammasome responses. Genetic variants in both pathways are associated with increased IBD susceptibility. Defective autophagy in dendritic cells, through gene knockdown or carriage of disease risk alleles in ATG16L1 , IRGM or NOD2 , alters antigen presentation and enhances T‐cell stimulation. ER stress activates autophagy through stimulation of the unfolded protein response mediated by XBP1. Disease‐associated alleles of XBP1 are implicated in Paneth cell dysfunction and decreased xenophagy.

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In Vivo Requirement for Atg5 in Antigen Presentation by Dendritic Cells

Cited by 436 publications

References 62 publications

Intersection of autophagy with pathways of antigen presentation

Intersection of autophagy with pathways of antigen presentation

A comparative proteomics study of a synovial cell line stimulated with TNF‐α

Role of Autophagy‐Related Genes in the Pathology of Inflammatory Bowel Disease

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