Notch controls effector CD8+ T cell differentiation

Duval, Frédéric; Mathieu, Mélissa; Labrecque, Nathalie

doi:10.18632/oncotarget.4886

Cited by 6 publications

(6 citation statements)

References 7 publications

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“…Although resting human CD8 + T cells also harbor all complosome components so far detected in CD4 + T cells (; Figure 1) and, equally, express Notch‐1/2, it remains to be determined whether C3a/complosome activity and the CD46 cross talk with the Notch system serves a similar homeostatic role in CTLs.…”

Section: The Complosome In Human T Cell Metabolismmentioning

confidence: 95%

Complement and human T cell metabolism: Location, location, location

West

Kunz

Kemper

2020

Immunological Reviews

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Immunological Reviews. 2020;295:68-81. wileyonlinelibrary.com/journal/imr 1 | INTRODUC TI ON Our contemporary immune system has evolved under the constant pressure from a broad range of pathogens that manipulate the host to enhance their own propagation. As diverse as the pathogenic threats are, ranging from intra-and extracellular bacteria, viruses, fungi, and complex parasites, as elegant and effective are the defense mechanisms developed and employed by the host to combat this constant onslaught. Particularly, the detection systems that are functioning as the first lines of defense against such invaders are formidable. If a microbe has managed to penetrate the protective physical barriers, such as the skin, or lung, a range of innate immune sensors either circulating in the blood, lymph, and interstitial fluids or expressed in and on scavenger and sentinel cells, such as neutrophils and microphages, detect the conserved pathogen-associated molecular patterns (PAMPs). These sensor systems comprise several pattern recognition receptors (PRRs) and include the Toll-like receptors (TLRs), the NOD-like receptors (NLRs), the retinoic acid-inducible gene-I (RIG)-like system, several distinct inflammasomes, and the complement system-derived receptors. 1,2 Activation of PRRs by a pathogen is most often triggered in several sensor systems in parallel and then initiates the general inflammatory reaction as well as tailored immune cell activation specifically effective toward the identified pathogen. The ability of PRR systems to decisively discriminate between a real threat, that is non-self and dangerous self via recognizing so-called danger-associated molecular patterns (DAMPs), and self and harmless alterations of self is critical for our health. Thus, there are several checks and balances build into the PRR systems that prevent unwanted reactions against sensed AbstractThe complement system represents one of the evolutionary oldest arms of our immune system and is commonly recognized as a liver-derived and serum-active system critical for providing protection against invading pathogens. Recent unexpected findings, however, have defined novel and rather "uncommon" locations and activities of complement. Specifically, the discovery of an intracellularly active complement system-the complosome-and its key role in the regulation of cell metabolic pathways that underly normal human T cell responses have taught us that there is still much to be discovered about this system. Here, we summarize the current knowledge about the emerging functions of the complosome in T cell metabolism. We further place complosome activities among the non-canonical roles of other intracellular innate danger sensing systems and argue that a "location-centric" view of complement evolution could logically justify its close connection with the regulation of basic cell physiology. K E Y W O R D S CD46, complement, complosome, metabolism, T cells | 69 WEST ET al.innocuous antigens. However, PRRs not only take care to contain tissue injury during their...

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Section: The Complosome In Human T Cell Metabolismmentioning

confidence: 95%

Complement and human T cell metabolism: Location, location, location

West

Kunz

Kemper

2020

Immunological Reviews

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“…Additionally, the influenza virus has been shown to block the Notch ligand Delta-like 1 (DLL1) causing a heightened inflammatory response and decreased interferon-c levels, which leads to compromised immunity against the virus. In contrast, macrophages were found to enhance their DLL1 production during the course of infection to protect against the same virus ( 32 , 33 , 65 ). In the case of COVID-19, an interesting enzyme that could be linking Notch and COVID-19 activation is FURIN.…”

Section: The Beginning (Viral Entry)mentioning

confidence: 97%

The Notch Pathway: A Link Between COVID-19 Pathophysiology and Its Cardiovascular Complications

Breikaa

Lilly

2021

Front. Cardiovasc. Med.

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COVID-19 is associated with a large number of cardiovascular sequelae, including dysrhythmias, myocardial injury, myocarditis and thrombosis. The Notch pathway is one likely culprit leading to these complications due to its direct role in viral entry, inflammation and coagulation processes, all shown to be key parts of COVID-19 pathogenesis. This review highlights links between the pathophysiology of SARS-CoV2 and the Notch signaling pathway that serve as primary drivers of the cardiovascular complications seen in COVID-19 patients.

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“…Enrichment analysis revealed that high A 2A R expression primarily increased with genes involved in the Notch pathway and Th1 and Th2 differentiation. The Notch pathway directly upregulates granzyme B and perforin mRNA expression, promotes differentiation into effector cells, and maintains memory T cells [ 36 , 37 , 38 ]. In addition, notch deletion results in CD8+ T cell dysfunction and antitumor immunity impairment, whereas stimulation of the notch pathway can increase tumor suppression [ 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

A2AR as a Prognostic Marker and a Potential Immunotherapy Target in Human Glioma

Rafii

Ghouzlani

Naji

et al. 2023

IJMS

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Gliomas are considered one of the most malignant tumors in the body. The immune system has the ability to control the initiation and development of tumors, including gliomas. Thus, immune cells find themselves controlled by various molecular pathways, inhibiting their activation, such as the immunosuppressive adenosine 2A receptor (A2AR). Our objective was to establish the expression profile and role of A2AR at the transcriptomic level, using real-time RT-PCR in Moroccan glioma patients, in addition to TCGA and CGGA cohorts. The real-time RT-PCR results in Moroccan patients showed that high expression of this gene was associated with poor survival in males. Our study on the CGGA cohort corroborated these results. In addition, there was a positive association of A2AR with T-cell exhaustion genes. A2AR also correlated strongly with genes that are primarily enriched in focal adhesion and extracellular matrix interactions, inducing epithelial mesenchymal transition, angiogenesis, and glioma growth. However, in the TCGA cohort, the A2AR showed results that were different from the two previously examined cohorts. In fact, this gene was instead linked to a good prognosis in patients with the astrocytoma histological type. The correlation and enrichment results reinforced the prognostic role of A2AR in this TCGA cohort, in which its high expression was shown to be related to lymphocyte differentiation and a successful cytolytic response, suggesting a more efficient anti-tumor immune response. Correlations and differential analyses based on A2AR gene expression, to understand the cause of the association of this gene with two different prognoses (CGGA males and TCGA Astrocytoma), showed that the overexpression of A2AR in Chinese male patients could be associated with the overexpression of extracellular adenosine, which binds to A2AR to induce immunosuppression and consequently a poor prognosis. However, in the second group (TCGA astrocytomas), the overexpression of the gene could be associated with an adenosine deficiency, and therefore this receptor does not undergo activation. The absence of A2AR activation in these patients may have protected them from immunosuppression, which could reflect the good prognosis. A2AR can be considered a promising therapeutic target in male CGGA and Moroccan patients with gliomas.

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Notch controls effector CD8+ T cell differentiation

Cited by 6 publications

References 7 publications

Complement and human T cell metabolism: Location, location, location

Complement and human T cell metabolism: Location, location, location

The Notch Pathway: A Link Between COVID-19 Pathophysiology and Its Cardiovascular Complications

A2AR as a Prognostic Marker and a Potential Immunotherapy Target in Human Glioma

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