Following traumatic peripheral nerve injury, adequate restoration of function remains an elusive clinical goal. Recent research highlights the complex role that the immune system plays in both nerve injury and regeneration. Pro-regenerative processes in wounded soft tissues appear to be significantly mediated by cytokines of the type 2 immune response, notably interleukin (IL)-4. While IL-4 signaling has been firmly established as a critical element in general tissue regeneration during wound healing, it has also emerged as a critical process in nerve injury and regeneration. In this context of peripheral nerve injury, endogenous IL-4 signaling has recently been confirmed to influence more than leukocytes, but including also neurons, axons, and Schwann cells. Given the role IL-4 plays in nerve injury and regeneration, exogenous IL-4 and/or compounds targeting this signaling pathway have shown encouraging preliminary results to treat nerve injury or other neuropathy in rodent models. In particular, the exogenous stimulation of the IL-4 signaling pathway appears to promote postinjury neuron survival, axonal regeneration, remyelination, and thereby improved functional recovery. These preclinical data strongly suggest that targeting IL-4 signaling pathways is a promising translational therapy to augment treatment approaches of traumatic nerve injury. However, a better understanding of the type 2 immune response and associated signaling networks functioning within the nerve injury microenvironment is still needed to fully develop this promising therapeutic avenue.

在外伤性周围神经损伤后，充分恢复功能仍然是一个难以实现的临床目标。最近的研究强调了免疫系统在神经损伤和再生中的复杂作用。受伤软组织中的促再生过程似乎是由 2 型免疫反应的细胞因子，特别是白细胞介素 (IL)-4 介导的。虽然 IL-4 信号已被确定为伤口愈合过程中一般组织再生的关键因素，但它也已成为神经损伤和再生的关键过程。在周围神经损伤的背景下，最近证实内源性 IL-4 信号传导不仅影响白细胞，还包括神经元、轴突和雪旺氏细胞。鉴于 IL-4 在神经损伤和再生中的作用，针对该信号通路的外源性 IL-4 和/或化合物已显示出令人鼓舞的初步结果，可治疗啮齿动物模型中的神经损伤或其他神经病变。特别是，IL-4 信号通路的外源性刺激似乎促进了损伤后神经元存活、轴突再生、髓鞘再生，从而改善了功能恢复。这些临床前数据强烈表明，靶向 IL-4 信号通路是一种很有前景的转化疗法，可增加创伤性神经损伤的治疗方法。然而，仍需要更好地了解在神经损伤微环境中起作用的 2 型免疫反应和相关信号网络，以充分开发这种有前途的治疗途径。