Image 3_ATP/P2X7 receptor signal aggravates ischemic stroke injury by activating Th17 cells via STAT3/IL-21 pathway.tif
Background<p>During cerebral ischemia, adenosine triphosphate (ATP) is released into the extracellular matrix from damaged neurons and glial cells, functioning as a danger signal. However, the involvement of ATP/P2X7 signaling in regulating the infiltrated lymphocytes during ischemia-reperfusi...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | , , , , , , , |
| Published: |
2025
|
| Subjects: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Background<p>During cerebral ischemia, adenosine triphosphate (ATP) is released into the extracellular matrix from damaged neurons and glial cells, functioning as a danger signal. However, the involvement of ATP/P2X7 signaling in regulating the infiltrated lymphocytes during ischemia-reperfusion (IR) injury remain unclear.</p>Methods<p>The expression level of P2X7 was evaluated in infiltrated lymphocytes from experimental stroke mice. To further elucidate the role of P2X7 signaling in infiltrated immune cells during ischemic stroke, P2X7-knockout (KO) mice and Rag2<sup>-/-</sup> mice were utilized. Additionally, in vitro experiments were conducted to explore the underlying mechanisms.</p>Results<p>Flow cytometry analysis revealed that the expression of P2X7 was mainly expressed in CD4<sup>+</sup>and CD8<sup>+</sup>T cells among the infiltrated lymphocytes in stroke lesions of the mice. P2X7-KO mice exhibited smaller infarct sizes and improved neurological function compared to wild-type mice. Rag2<sup>-/-</sup> mice that received P2X7-KO CD4<sup>+</sup>T cells demonstrated reduced ischemic-reperfusion injury and a decreased level of IL-17A and frequency of Th17 cells compared to Rag2<sup>-/-</sup> mice that received wild type CD4<sup>+</sup>T cells. Transcriptome sequencing and in vitro experiments indicate that P2X7 may mediate the expression of IL-21 and regulating the synthesis of IL-17A and the differentiation of Th17 cells. We also confirmed that P2X7 receptor regulates IL-21 through STAT3 signaling.</p>Conclusions<p>Our findings suggest that the loss of ATP/P2X7 signaling in CD4<sup>+</sup>T cells may inhibit the pSTAT3, IL-21 pathway, leading to reduced differentiation of Th17 cells and ultimately mitigating IR injury. This provides novel insights into the role of ATP/P2X7-mediated signaling in T cell inflammation during ischemic stroke.</p> |
|---|