After skin allotransplantation, intercellular transfer of donor MHC molecules mediated primarily by extracellular vesicles (EVs) released by the allograft is known to contribute to semi-direct and indirect activation of alloreactive T cells involved in graft rejection. At the same time, there is ample evidence showing that initiation of adaptive alloimmunity depends on early innate inflammation caused by tissue injury and subsequent activation of myeloid cells (macrophages and dendritic cells) recognizing danger associated molecular patterns (DAMPs). Among these DAMPs, extracellular ATP plays a key role in innate inflammation through binding to P2X7 receptors. Indeed, this process leads to the activation of the NLRP3 inflammasome and subsequent production and release of inflammatory cytokines and EVs. This prompted us to evaluate the influence of innate inflammation triggered by ATP-mediated signaling of P2X7 receptors on EV release by donor cells after skin transplantation in mice. In this article, we show that inhibition of P2X7R signaling suppresses both EV release and MHC cross-decoration of leukocytes and prolongs skin allograft survival in mice. This study reveals a novel aspect of the role of innate immunity in allotransplantation.

中文翻译：

---

ATP 介导的 P2X7 受体信号转导控制同种异体移植后供体细胞外囊泡释放和 MHC 交叉装饰。


皮肤同种异体移植后，已知主要由同种异体移植物释放的细胞外囊泡 （EV） 介导的供体 MHC 分子的细胞间转移有助于参与移植物排斥反应的同种异体反应性 T 细胞的半直接或间接激活。同时，有充分的证据表明，适应性同种异体免疫的启动取决于组织损伤引起的早期先天性炎症和随后的髓系细胞（巨噬细胞和树突状细胞）识别危险相关分子模式 （DAMP） 的激活。在这些 DAMP 中，细胞外 ATP 通过与 P2X7 受体结合在先天性炎症中起关键作用。事实上，这个过程导致 NLRP3 炎性小体的激活以及随后炎性细胞因子和 EV 的产生和释放。这促使我们评估 ATP 介导的 P2X7 受体信号传导触发的先天炎症对小鼠皮肤移植后供体细胞释放 EV 的影响。在本文中，我们表明抑制 P2X7R 信号传导抑制白细胞的 EV 释放和 MHC 交叉装饰，并延长小鼠皮肤同种异体移植物的存活时间。这项研究揭示了先天免疫在同种异体移植中作用的一个新方面。