CD4 T cell autophagy is integral to memory maintenance

Murera, Diane; Arbogast, Florent; Arnold, Johan; Bouis, Delphine; Muller, Sylviane; Gros, Frédéric

doi:10.1038/s41598-018-23993-0

Cited by 50 publications

(46 citation statements)

References 23 publications

(27 reference statements)

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“…In such models, as mentioned before, one could argue that the higher ROS production and cell death observed in mature populations could be for part due to defects accumulated during their developmental phases. After deletion occurring only in mature T cells ( 56 ), we confirm CD8 + T cells sensibility to ROS linked to defective mitophagy, which is not shared by CD4 + T cells. Altogether, these data demonstrate a superior need for mitophagy prior to their activation in CD8 + than in CD4 + T cells.…”

Section: Autophagy In Peripheral T Cellssupporting

confidence: 59%

“…Several reports demonstrated a higher sensitivity of CD8 + T cells to macroautophagy loss, compared to CD4 T cells ( 39 , 45 , 56 ). Interestingly, CD8 T cells possess a lower mitochondrial load than their CD4 counterpart.…”

Section: Autophagy In Peripheral T Cellsmentioning

confidence: 98%

“…This could also be true for memory CD4 + T cells. We have described that autophagy-deficient CD4 T + cell accumulate neutral lipids, which could be linked to defective lipophagy ( 56 ).…”

Section: Autophagy In Peripheral T Cellsmentioning

confidence: 99%

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Lymphocyte Autophagy in Homeostasis, Activation, and Inflammatory Diseases

Arbogast

Gros

2018

Front. Immunol.

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Autophagy is a catabolic mechanism, allowing the degradation of cytoplasmic content via lysosomal activity. Several forms of autophagy are described in mammals. Macroautophagy leads to integration of cytoplasmic portions into vesicles named autophagosomes that ultimately fuse with lysosomes. Chaperone-mediated autophagy is in contrast the direct translocation of protein in lysosomes. Macroautophagy is central to lymphocyte homeostasis. Although its role is controversial in lymphocyte development and in naive cell survival, it seems particularly involved in the maintenance of certain lymphocyte subtypes. Its importance in memory B and T cells biology has recently emerged. Moreover, some effector cells like plasma cells rely on autophagy for survival. Autophagy is central to glucose and lipid metabolism, and to the maintenance of organelles like mitochondria and endoplasmic reticulum. In addition macroautophagy, or individual components of its machinery, are also actors in antigen presentation by B cells, a crucial step to receive help from T cells, this crosstalk favoring their final differentiation into memory or plasma cells. Autophagy is deregulated in several autoimmune or autoinflammatory diseases like systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and Crohn’s disease. Some treatments used in these pathologies impact autophagic activity, even if the causal link between autophagy regulation and the efficiency of the treatments has not yet been clearly established. In this review, we will first discuss the mechanisms linking autophagy to lymphocyte subtype survival and the signaling pathways involved. Finally, potential impacts of autophagy modulation in lymphocytes on the course of these diseases will be approached.

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Section: Autophagy In Peripheral T Cellssupporting

confidence: 59%

Section: Autophagy In Peripheral T Cellsmentioning

confidence: 98%

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Lymphocyte Autophagy in Homeostasis, Activation, and Inflammatory Diseases

Arbogast

Gros

2018

Front. Immunol.

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“…In inflammatory contexts, such as asthma, CD4 + T cells can play into both T H 17 and T H 2 type mediated inflammation ( 138 ) and have also been shown to utilize autophagy ( 139 ). Like their CD8 + counterparts, CD4 + T cells have also been found to have extensive autophagy involved in a variety of cellular functions, such as metabolism and memory ( 112 ). During activation, autophagy is massively upregulated in CD4 + T cells ( 122 , 140 ).…”

Section: Role Of Autophagy In Lymphoid Cellsmentioning

confidence: 99%

Role of Autophagy in Lung Inflammation

2020

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Autophagy is a cellular recycling system found in almost all types of eukaryotic organisms. The system is made up of a variety of proteins which function to deliver intracellular cargo to lysosomes for formation of autophagosomes in which the contents are degraded. The maintenance of cellular homeostasis is key in the survival and function of a variety of human cell populations. The interconnection between metabolism and autophagy is extensive, therefore it has a role in a variety of different cell functions. The disruption or dysfunction of autophagy in these cell types have been implicated in the development of a variety of inflammatory diseases including asthma. The role of autophagy in non-immune and immune cells both lead to the pathogenesis of lung inflammation. Autophagy in pulmonary non-immune cells leads to tissue remodeling which can develop into chronic asthma cases with long term effects. The role autophagy in the lymphoid and myeloid lineages in the pathology of asthma differ in their functions. Impaired autophagy in lymphoid populations have been shown, in general, to decrease inflammation in both asthma and inflammatory disease models. Many lymphoid cells rely on autophagy for effector function and maintained inflammation. In stark contrast, autophagy deficient antigen presenting cells have been shown to have an activated inflammasome. This is largely characterized by a T H 17 response that is accompanied with a much worse prognosis including granulocyte mediated inflammation and steroid resistance. The cell specificity associated with changes in autophagic flux complicates its targeting for amelioration of asthmatic symptoms. Differing asthmatic phenotypes between T H 2 and T H 17 mediated disease may require different autophagic modulations. Therefore, treatments call for a more cell specific and personalized approach when looking at chronic asthma cases. Viral-induced lung inflammation, such as that caused by SARS-CoV-2, also may involve autophagic modulation leading to inflammation mediated by lung resident cells. In this review, we will be discussing the role of autophagy in non-immune cells, myeloid cells, and lymphoid cells for their implications into lung inflammation and asthma. Finally, we will discuss autophagy's role viral pathogenesis, immunometabolism, and asthma with insights into autophagic modulators for amelioration of lung inflammation.

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“…While apparently dispensable for B-cell development, it was claimed that macroautophagy plays a major role in plasma cell survival, B-cell receptor trafficking and antigen presentation, and long-term autoantibody secretion [ 10 , 11 ]. Macroautophagy is also centrally involved in the maintenance and survival of memory CD4 and CD8 T cells with foreseeable consequences on the autoimmune response [ 12 ]. The underlying reasons for macroautophagy dysfunctions in lupus are not known but several independent investigations have identified risk loci spanning autophagy-linked genes in lupus patients [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Remodeling of Altered Autophagy-Lysosomal Pathway by a Phosphopeptide in Lupus

Wang

Tasset

Cuervo

et al. 2020

Cells

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The phosphopeptide P140/Lupuzor, which improves the course of lupus disease in mice and patients, targets chaperone-mediated autophagy (CMA), a selective form of autophagy that is abnormally upregulated in lupus-prone MRL/lpr mice. Administered intravenously to diseased mice, P140 reduces the expression level of two major protein players of CMA, LAMP2A and HSPA8, and inhibits CMA in vitro in a cell line that stably expresses a CMA reporter. Here, we aimed to demonstrate that P140 also affects CMA in vivo and to unravel the precise cellular mechanism of how P140 interacts with the CMA process. MRL/lpr mice and CBA/J mice used as control received P140 or control peptides intravenously. Lysosome-enriched fractions of spleen or liver were prepared to examine lysosomal function. Highly purified lysosomes were further isolated and left to incubate with the CMA substrate to study at which cellular step P140 interacts with the CMA process. The data show that P140 effectively regulates CMA in vivo in MRL/lpr mice at the step of substrate lysosomal uptake and restores some alterations of defective lysosomes. For the first time, it is demonstrated that by occluding the intralysosome uptake of CMA substrates, a therapeutic molecule can attenuate excessive CMA activity in a pathological pro-inflammatory context and protect against hyperinflammation. This recovery effect of P140 on hyperactivated CMA is not only important for lupus therapy but potentially also for treating other (auto)inflammatory diseases, including neurologic and metabolic disorders, where CMA modulation would be highly beneficial.

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CD4 T cell autophagy is integral to memory maintenance

Cited by 50 publications

References 23 publications

Lymphocyte Autophagy in Homeostasis, Activation, and Inflammatory Diseases

Lymphocyte Autophagy in Homeostasis, Activation, and Inflammatory Diseases

Role of Autophagy in Lung Inflammation

In Vivo Remodeling of Altered Autophagy-Lysosomal Pathway by a Phosphopeptide in Lupus

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