A truncation variant of the cation channel P2RX5 is upregulated during T cell activation
Pierre Abramowski1, Christoph Ogrodowczyk2, Roland Martin3
1Institute for Neuroimmunology and Clinical Multiple Sclerosis Research (inims), ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Research Department Cell and Gene Therapy, Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Abstract:
Members of the P2X family of ligand-gated cation channels (P2RX) are expressed by various cell types including neurons, smooth- and cardiac muscle cells, and leukocytes. The channels mediate signalling in response to extracellular ATP. Seven subunit isoforms (P2RX1-P2RX7) have been identified and these can assemble as homo- and heterotrimeric molecules. In humans, P2RX5 exists as a natural deletion mutant lacking amino acids 328-349 of exon 10, which are part of transmembrane (TM) 2 and pre-TM2 regions in other organisms like rat, chicken and zebrafish. We show that P2RX5 gene expression of human T lymphocytes is upregulated during activation. P2RX5 is recruited to the cell surface. P2RX5-siRNA-transfected CD4+ T cells produced twofold more IL-10 than controls. Surface and intracellular P2RX5 expression was upregulated in activated antigen-specific CD4+ T cell clones. These data indicate a functional role of the human P2RX5 splice variant in T cell activation and immunoregulation.
Insights
The human P2RX5 splice variant, a P2X receptor, is upregulated in activated T cells and influences IL-10 production, suggesting a role in immune regulation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- P2X receptors (P2RX) are ligand-gated cation channels responding to extracellular ATP.
- Seven P2RX subunit isoforms exist, forming homo- and heterotrimeric channels.
- Human P2RX5 is a natural deletion mutant affecting transmembrane regions.
Purpose of the Study:
- To investigate the role of the human P2RX5 splice variant in T cell activation.
- To determine the functional significance of P2RX5 in T cell immunoregulation.
Main Methods:
- Analyzing P2RX5 gene expression in activated human T lymphocytes.
- Utilizing siRNA to assess the impact of P2RX5 knockdown on IL-10 production.
- Quantifying surface and intracellular P2RX5 expression in activated T cell clones.
Main Results:
- P2RX5 gene expression is upregulated in human T lymphocytes upon activation.
- P2RX5 protein is recruited to the cell surface of activated T cells.
- P2RX5 knockdown in CD4+ T cells led to a twofold increase in IL-10 production.
- Activated antigen-specific CD4+ T cell clones showed increased P2RX5 expression.
Conclusions:
- The human P2RX5 splice variant plays a functional role in T cell activation.
- P2RX5 influences T cell immunoregulation, specifically affecting IL-10 secretion.
Related Concept Videos
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:24B Cell Activation and Differentiation
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
01:09GPCRs Regulate Adenylyl Cylase Activity