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The posttraumatic activation of CD4+ T regulatory cells is modulated by TNFR2- and TLR4-dependent pathways, but not by IL-10

机译:CD4 + T调节细胞的错误激活由TNFR2和TLR4依赖性途径调节,但不是由IL-10调节

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摘要

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. One sentence summaryTLR4- and TNFR2-dependent mechanisms, but not IL-10-dependent pathways, modulate the anti-inflammatory response of CD4+ Tregs following trauma.
机译:通过与CD4 + T调节细胞(CD4 + Tregs)相互作用,血小板调节损伤后的免疫系统。潜在机制仍未解决。我们通过肿瘤坏死因子-α(TNFα) - ,等受体-4(TLR4) - ,和白细胞介素-10(IL-10)的损伤的肺碱相互作用。在鼠烧伤损伤模型中,选择性地处理CD4 + Treg激活途径。 TNFR2,TLR4和IL-10缺乏小鼠。使用磷粉流式细胞术分析CD4 + Treg信号分子PKC-θ以检测快速细胞活化。用于评估血小板活化的血栓发球菌IL-10串扰的破坏没有显着影响。选择性破坏旁静脉相互作用与宫外止血参数的变化有关.TNFR2和TLR4依赖性途径调节创伤后CD4 + Tregs的活化。相比之下,我们没有观察到IL-10在CD4 + Tregs的错误激活中的作用。一句术语概述TN和TNFR2依赖性机制,但不是IL-10依赖性途径,调节创伤后CD4 + Tregs的抗炎响应。

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