Frontline Science: P2Y11 receptors support T cell activation by directing mitochondrial trafficking to the immune synapse

Ledderose, Carola; Bromberger, Sophie; Slubowski, Christian J.; Sueyoshi, Koichiro; Junger, Wolfgang G.

doi:10.1002/jlb.2hi0520-191r

Cited by 18 publications

(13 citation statements)

References 67 publications

(156 reference statements)

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“…In neurons, cAMP promotes directional movement of mitochondria along the microtubule network ( 79 – 82 ), while local cytosolic Ca 2+ hotspots act as mitochondrial stop signals ( 83 ). Our recent work has shown that P2Y11 receptors promote trafficking of mitochondria to the IS of T cells ( 84 ). Thus, P2Y11 and P2X4 receptors jointly recruit and activate mitochondria at the IS in order to sustain T cell activation.…”

Section: P2y11 and P2x4 Receptors Orchestrate The Accumulation And Acmentioning

confidence: 99%

Mitochondria Synergize With P2 Receptors to Regulate Human T Cell Function

Ledderose

Junger

2020

Front. Immunol.

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Intracellular ATP is the universal energy carrier that fuels many cellular processes. However, immune cells can also release a portion of their ATP into the extracellular space. There, ATP activates purinergic receptors that mediate autocrine and paracrine signaling events needed for the initiation, modulation, and termination of cell functions. Mitochondria contribute to these processes by producing ATP that is released. Here, we summarize the synergistic interplay between mitochondria and purinergic signaling that regulates T cell functions. Specifically, we discuss how mitochondria interact with P2X1, P2X4, and P2Y11 receptors to regulate T cell metabolism, cell migration, and antigen recognition. These mitochondrial and purinergic signaling mechanisms are indispensable for host immune defense. However, they also represent an Achilles heel that can render the host susceptible to infections and inflammatory disorders. Hypoxia and mitochondrial dysfunction deflate the purinergic signaling mechanisms that regulate T cells, while inflammation and tissue damage generate excessive systemic ATP levels that distort autocrine purinergic signaling and impair T cell function. An improved understanding of the metabolic and purinergic signaling mechanisms that regulate T cells may lead to novel strategies for the diagnosis and treatment of infectious and inflammatory diseases.

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Section: P2y11 and P2x4 Receptors Orchestrate The Accumulation And Acmentioning

confidence: 99%

Mitochondria Synergize With P2 Receptors to Regulate Human T Cell Function

Ledderose

Junger

2020

Front. Immunol.

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“…P2X1R and P2X4R trigger a localized Ca 2+ influx that stimulates OXPHOS and propagates TCR-induced signalling, culminating in cytokine secretion and T-cell proliferation [ 86 ]. Junger and co-workers recently showed that mitochondrial trafficking to the immune synapse is directed by P2Y 11 Rs [ 87 ], suggesting that these receptors cooperate with P2X4Rs to recruit and stimulate mitochondria at the IS. P2X4Rs and P2Y 11 Rs fulfil similar roles in promoting T-cell migration.…”

Section: P2 Receptors In T-cell Signalling and Metabolic Regulationmentioning

confidence: 99%

P2 Receptors: Novel Disease Markers and Metabolic Checkpoints in Immune Cells

Vultaggio-Poma

Virgilio

2022

Biomolecules

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Extracellular ATP (eATP) and P2 receptors are novel emerging regulators of T-lymphocyte responses. Cellular ATP is released via multiple pathways and accumulates at sites of tissue damage and inflammation. P2 receptor expression and function are affected by numerous single nucleotide polymorphisms (SNPs) associated with diverse disease conditions. Stimulation by released nucleotides (purinergic signalling) modulates several T-lymphocyte functions, among which energy metabolism. Energy metabolism, whether oxidative or glycolytic, in turn deeply affects T-cell activation, differentiation and effector responses. Specific P2R subtypes, among which the P2X7 receptor (P2X7R), are either up- or down-regulated during T-cell activation and differentiation; thus, they can be considered indexes of activation/quiescence, reporters of T-cell metabolic status and, in principle, markers of immune-mediated disease conditions.

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“…Together with the involvement of other interconnected organelles, mitochondria activated the cyclic guanosine monophosphate synthetase (cGAS)-stimulator of interferon genes (STING) signaling pathway, leading to the production of host defense type I IFNs and pro-inflammatory cytokines (211). Therefore, beyond producing the ATP that was released and necessary for driving systemic inflammation (39), mitochondria interacted with P2X1, P2X4 and P2Y 11 receptors to regulate T cell metabolism (212), migration (213) and activation (214); emphasizing the important role of purinergic signalling pathways in persistent neuroinflammation (215).…”

Section: Purinergic Targets For Sars-cov-2 Induced Pathologiesmentioning

confidence: 99%

The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2

2022

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A long-shared evolutionary history is congruent with the multiple roles played by purinergic signaling in viral infection, replication and host responses that can assist or hinder viral functions. An overview of the involvement of purinergic signaling among a range of viruses is compared and contrasted with what is currently understood for SARS-CoV-2. In particular, we focus on the inflammatory and antiviral responses of infected cells mediated by purinergic receptor activation. Although there is considerable variation in a patient’s response to SARS-CoV-2 infection, a principle immediate concern in Coronavirus disease (COVID-19) is the possibility of an aberrant inflammatory activation causing diffuse lung oedema and respiratory failure. We discuss the most promising potential interventions modulating purinergic signaling that may attenuate the more serious repercussions of SARS-CoV-2 infection and aspects of their implementation.

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Frontline Science: P2Y11 receptors support T cell activation by directing mitochondrial trafficking to the immune synapse

Cited by 18 publications

References 67 publications

Mitochondria Synergize With P2 Receptors to Regulate Human T Cell Function

Mitochondria Synergize With P2 Receptors to Regulate Human T Cell Function

P2 Receptors: Novel Disease Markers and Metabolic Checkpoints in Immune Cells

The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2

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