Checking the garbage bin for problems in the house, or how autophagy assists in antigen presentation to the immune system

Romão, Susana; Gannagé, Monique; Münz, Christian

doi:10.1016/j.semcancer.2013.03.001

Cited by 32 publications

(25 citation statements)

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“…For this purpose, MHC class Ⅰ molecules get primarily loaded with proteasomal products for CD8 + T cell recognition, while MHC class Ⅱ molecules receive fragments of lysosomal degradation for CD4 + T cell recognition (Blum et al, 2013). Autophagy delivers cytoplasmic constituents for lysosomal hydrolysis, thereby contributing to endogenous antigen processing for MHC class Ⅱ presentation (Figure 4) (Romao et al, 2013a). This was first noted for a prominent CD4 + T cell antigen of the Epstein Barr virus (EBV) (Paludan et al, 2005;Leung et al, 2010).…”

Section: Endogenous Antigen Processing For Mhc Class ⅱ Presentationmentioning

confidence: 99%

Autophagy and autophagy-related proteins in the immune system

et al. 2015

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Autophagy is an intracellular bulk degradation system that is highly conserved in eukaryotes. The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes. In addition, studies have revealed other roles for the autophagic machinery beyond autophagy. In this Review, we introduce advances in the knowledge of the roles of autophagy and its components in immunity, including innate immunity, inflammatory responses and adaptive immunity. AbstractAutophagy is an intracellular bulk degradation system that is highly conserved in eukaryotes.The discovery of Atg proteins in the 1990s has greatly advanced our mechanistic understanding of autophagy, which allowed us to understand that autophagy plays important roles in various biological processes. In addition, recent studies revealed other roles of the autophagic machinery beyond autophagy. In this review, we introduce recent advances in our knowledge of the roles that autophagy and its components play in immunity, including innate immunity, inflammation responses, and adaptive immunity.

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Section: Endogenous Antigen Processing For Mhc Class ⅱ Presentationmentioning

confidence: 99%

Autophagy and autophagy-related proteins in the immune system

et al. 2015

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“…In recent years, the process of autophagy has been implicated in controlling antigen processing (4). Autophagy is a conserved catabolic process that maintains cellular energy homeostasis in response to a wide spectrum of cellular stresses (5,6).…”

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Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8α⁺dendritic cells

Parekh

Kumar

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34-deficient mice to assess the contribution of Vps34 to DC functions. We found that DCs from these animals have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways. Surprisingly, these animals displayed a defect in the homeostatic maintenance of splenic CD8α + DCs and in the capacity of these cells to cross-present cell corpse-associated antigens to MHC class I-restricted T cells, a property that was associated with defective expression of the T-cell Ig mucin (TIM)-4 receptor. Importantly, mice deficient in the Vps34-associated protein Rubicon, which is critical for a noncanonical form of autophagy called "Lightchain 3 (LC3)-associated phagocytosis" (LAP), lacked such defects. Finally, consistent with their defect in the cross-presentation of apoptotic cells, DC-specific Vps34-deficient animals developed increased metastases in response to challenge with B16 melanoma cells. Collectively, our studies have revealed a critical role of Vps34 in the regulation of CD8α + and CD4 + T cells, respectively. MHC class II-associated peptides are typically generated by proteolysis of endocytosed proteins (1), whereas MHC class I-associated peptides are predominantly generated by proteolysis of cytosolic proteins (2). However, in specialized antigen-presenting cells (APCs) such as a DC subset expressing CD8α and CD103, extracellular antigens can be presented in the context of MHC class I molecules via a cross-presentation pathway whose mechanism is incompletely understood (3).In recent years, the process of autophagy has been implicated in controlling antigen processing (4). Autophagy is a conserved catabolic process that maintains cellular energy homeostasis in response to a wide spectrum of cellular stresses (5, 6). Autophagy ensures continuous degradation of long-lived proteins, damaged cellular organelles, and protein aggregates to facilitate recycling of nutrients and hence promote cellular metabolism. The formation of autophagosomes requires an interplay between autophagyrelated (Atg) gene products, which have been well characterized in yeast and are conserved in mammals (7). Defective autophagy in mammalian cells results in the accumulation of damaged cellular organelles and protein aggregates, leading to stress with pathological consequences (8). Autophagy has common features with endocytosis, with which it shares effector molecules (9). However, how these processes and their shared machinery regulate antigen presentation remains incompletely understood.Vacuolar protein sorting 34 (Vps34) is a class III PI3K that plays a role in endocytosis, intracellular vesicular trafficking, and autophagosome formation during autophagy (10). Vps34-deficient cells display defec...

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“…Moreover, it contributes to antigen presentation by both major histocompatibility complex (MHC) class I and class II molecules. 2 Macroautophagy is also tightly linked to lymphocyte activation and survival. It has central roles in T-cell basal homeostasis, survival, and polarization.…”

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Autophagy is dispensable for B-cell development but essential for humoral autoimmune responses

Arnold¹,

Murera²,

Arbogast³

et al. 2015

Cell Death Differ

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To gain new insight into the role of B-cell autophagy, we generated two novel mouse models deficient for the autophagy-related gene (Atg)5, one from the outset pro-B cell stage (Atg5 f/ − Mb1 cre) and the other in mature B cells only (Atg5 f/ − CD21 cre). We show that autophagy is dispensable for pro-to pre-B cell transition, but necessary at a basal level to maintain normal numbers of peripheral B cells. It appears non-essential for B-cell activation under B-cell receptor stimulation but required for their survival after lipopolysaccharide stimulation that drives plasmablast differentiation and for specific IgM production after immunization. Results obtained using Atg5 f/ − CD21 cre × C57BL/6 lpr/lpr autoimmune-prone mice show that B-cell autophagy is involved in the maintenance of anti-nuclear antibody secretion, elevated number of long-lived plasma cells, and sustains IgG deposits in the kidneys. Thus, treatments specifically targeting autophagy might be beneficial in systemic autoimmune diseases. Cell Death and Differentiation (2016) 23, 853-864; doi:10.1038/cdd.2015 published online 20 November 2015 Macroautophagy is a catabolic process allowing the degradation of cytoplasmic material in double membrane vesicles, ultimately fusing with lysosomes. Macroautophagy, initially implicated in the generation of nutrients under metabolic stress, is known to have multiple roles, in different physiologic compartments, such as in vacuole trafficking, cell signalling, and cell death. Macroautophagy is deeply involved in the regulation of immunity.1 It has been shown that autophagy can regulate inflammation related to inflammasome activation and to type I interferon secretion. Moreover, it contributes to antigen presentation by both major histocompatibility complex (MHC) class I and class II molecules. 2Macroautophagy is also tightly linked to lymphocyte activation and survival. It has central roles in T-cell basal homeostasis, survival, and polarization.3 It is also involved in the regulation of T-cell signalling by downregulating the NF-κB pathway 4 and apoptosis processes through the procaspases 3 and 8 degradation. 5 Macroautophagy has additionally been described to regulate B-cell lineage, in particular during B-cell development. Thus, it has been shown that B cells generated from fetal liver chimaeras, with a complete deletion of the essential autophagy-related gene (Atg)5, exhibited a block at the proto pre-B stage transition.6,7 However, as the genetic deletion is systemic and occurs very early during development, the question remains over whether the developmental blockade could be due to defects resulting from early haematopoietic development. Indeed, macroautophagy has been shown to be fundamental to haematopoietic stem cell survival and renewal.8 Moreover, conditional deletion of Atg5 under the control of CD19 promoter expressed from the pre-B stage does not lead to major developmental breaks, except a decrease in B-1a B-cell population. 6 The contrast with results obtained with chimaeric mice could be due...

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Checking the garbage bin for problems in the house, or how autophagy assists in antigen presentation to the immune system

Cited by 32 publications

References 58 publications

Autophagy and autophagy-related proteins in the immune system

Autophagy and autophagy-related proteins in the immune system

Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8α⁺dendritic cells

Autophagy is dispensable for B-cell development but essential for humoral autoimmune responses

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Checking the garbage bin for problems in the house, or how autophagy assists in antigen presentation to the immune system

Cited by 32 publications

References 58 publications

Autophagy and autophagy-related proteins in the immune system

Autophagy and autophagy-related proteins in the immune system

Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8α+dendritic cells

Autophagy is dispensable for B-cell development but essential for humoral autoimmune responses

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Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8α⁺dendritic cells