P2X7 is expressed on human innate-like T lymphocytes and mediates susceptibility to ATP-induced cell death
Riekje Winzer1, Arnau Serracant-Prat1, Valerie J Brock2
1Department of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Abstract:
Extracellular ATP activates the P2X7 receptor, leading to inflammasome activation and release of pro-inflammatory cytokines in monocytes. However, a detailed analysis of P2X7 receptor expression and function in the human T cell compartment has not been reported. Here, we used a P2X7-specific nanobody to assess cell membrane expression and function of P2X7 on peripheral T lymphocyte subsets. The results show that innate-like T cells, which effectively react to innate stimuli by secreting high amounts of pro-inflammatory cytokines, have the highest expression of P2X7 in the human T cell compartment. Using Tγδ cells as example for an innate-like lymphocyte population, we demonstrate that these cells are more sensitive to P2X7 receptor activation than conventional T cells, affecting fundamental cellular mechanisms like calcium signaling and ATP-induced cell death. The increased susceptibility of innate-like T cells to P2X7-mediated cell death provides a mechanism to control their homeostasis under inflammatory conditions. Understanding the expression and function of P2X7 on human immune cells is essential to assume the benefits and consequences of newly developed P2X7-based therapeutic approaches.
Insights
Innate-like T cells, particularly Tγδ cells, exhibit higher P2X7 receptor expression and sensitivity. This impacts calcium signaling and cell death, offering insights into immune homeostasis and P2X7-based therapies.
Area of Science:
- Immunology
- Cell Biology
Background:
- Extracellular ATP (eATP) signals via P2X7 receptors, activating inflammasomes and pro-inflammatory cytokine release in monocytes.
- P2X7 receptor expression and function in human T cells remain largely uncharacterized.
Purpose of the Study:
- To investigate P2X7 receptor expression and function across human peripheral T lymphocyte subsets.
- To elucidate the role of P2X7 in innate-like T cells compared to conventional T cells.
Main Methods:
- Utilized a P2X7-specific nanobody for cell membrane expression analysis.
- Assessed P2X7 function by examining calcium signaling and ATP-induced cell death.
- Focused on Tγδ cells as a representative innate-like T cell population.
Main Results:
- Innate-like T cells demonstrate the highest P2X7 receptor expression within the human T cell compartment.
- Tγδ cells exhibit heightened sensitivity to P2X7 receptor activation compared to conventional T cells.
- P2X7 activation in Tγδ cells affects calcium signaling and induces cell death.
Conclusions:
- Elevated P2X7 expression and sensitivity in innate-like T cells suggest a role in regulating their homeostasis during inflammation.
- Findings are crucial for understanding the therapeutic potential and risks of P2X7-targeting drugs in immune modulation.
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