Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich. Ismaninger Strasse 22, 81675 Munich, Germany.
Department of Orthopedic Trauma, Hand-, Plastic-, and Reconstructive Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Cell Immunol. 2018 Sep;331:137-145. doi: 10.1016/j.cellimm.2018.06.009. Epub 2018 Jun 22.
Platelets modulate the immune system following injury by interacting with CD4+ T regulatory cells (CD4+ Tregs). The underlying mechanisms remain unsolved. We hypothesize paracrine interactions via Tumor necrosis factor-alpha (TNFα)-, Toll like receptor-4 (TLR4)-, and Interleukin-10 (IL-10). In the murine burn injury model, CD4+ Treg activation pathways were selectively addressed using TNFR2-, TLR4- and IL-10-deficient mice. The CD4+ Treg signalling molecule PKC-θ was analyzed using phospho-flow cytometry to detect rapid cell activation. Thromboelastometry (ROTEM®) was used to assess platelet activation. Injury induced significant early activation of CD4+ Tregs, disruption of TNFR2 and TLR4 activation pathways resulted in lower activity. The disruption of IL-10 crosstalk had no significant impact. Selective disruption of paracrine interactions is associated with changes in posttraumatic hemostasis parameters. TNFR2- and TLR4-dependent pathways modulate the activation of CD4+ Tregs following trauma. In contrast, we did not observe a role of IL-10 in the posttraumatic activation of CD4+ Tregs.
TLR4- and TNFR2-dependent mechanisms, but not IL-10-dependent pathways, modulate the anti-inflammatory response of CD4+ Tregs following trauma.
血小板通过与 CD4+T 调节细胞（CD4+Tregs）相互作用来调节损伤后的免疫系统。潜在的机制仍未解决。我们假设通过肿瘤坏死因子-α（TNFα）-、Toll 样受体 4（TLR4）-和白细胞介素 10（IL-10）的旁分泌相互作用。在小鼠烧伤损伤模型中，使用 TNFR2-、TLR4-和 IL-10 缺陷型小鼠选择性地解决 CD4+Treg 激活途径。使用磷酸化流式细胞术分析 CD4+Treg 信号分子 PKC-θ，以检测快速的细胞激活。血栓弹性描记术（ROTEM®）用于评估血小板激活。损伤诱导 CD4+Tregs 早期显著激活，破坏 TNFR2 和 TLR4 激活途径导致活性降低。IL-10 串扰的破坏没有显著影响。旁分泌相互作用的选择性破坏与创伤后止血参数的变化有关。TNFR2 和 TLR4 依赖性途径调节创伤后 CD4+Tregs 的激活。相比之下，我们没有观察到 IL-10 在创伤后 CD4+Tregs 激活中的作用。
TLR4 和 TNFR2 依赖性机制，但不是 IL-10 依赖性途径，调节创伤后 CD4+Tregs 的抗炎反应。
