The interleukin-6 (IL-6) family of cytokines and its downstream effector, STAT3, are important mediators of neuronal health, repair, and disease throughout the CNS, including the visual system. Here, we elucidate a transcription-independent mechanism for the neuropoietic activities of IL-6 related to axon development, regeneration, and repair. We examined the outcome of IL-6 deficiency on structure and function of retinal ganglion cell (RGC) axons, which form the optic projection. We found that IL-6 deficiency substantially delays anterograde axon transport in vivo. The reduced rate of axon transport is accompanied by changes in morphology, structure, and post-translational modification of microtubules. In vivo and in vitro studies in mice and swine revealed that IL-6-dependent microtubule phenotypes arise from protein-protein interactions between STAT3 and stathmin. As in tumor cells and T cells, this STAT3-stathmin interaction stabilizes microtubules in RGCs. Thus, this IL-6-STAT3-dependent mechanism for axon architecture is likely a fundamental mechanism for microtubule stability systemically.

白介素 6 (IL-6) 细胞因子家族及其下游效应子 STAT3 是整个中枢神经系统（包括视觉系统）神经元健康、修复和疾病的重要介质。在这里，我们阐明了与轴突发育、再生和修复相关的 IL-6 神经生成活性的转录非依赖性机制。我们检查了 IL-6 缺乏对形成光学投射的视网膜神经节细胞 (RGC) 轴突的结构和功能的影响。我们发现 IL-6 缺乏会显着延迟体内顺行轴突运输。轴突运输率的降低伴随着形态、结构和微管翻译后修饰的变化。体内和体外对小鼠和猪的研究表明，IL-6 依赖性微管表型源于 STAT3 和 stathmin 之间的蛋白质-蛋白质相互作用。与在肿瘤细胞和 T 细胞中一样，这种 STAT3-stathmin 相互作用可稳定 RGC 中的微管。因此，轴突结构的这种依赖于 IL-6-STAT3 的机制可能是系统微管稳定性的基本机制。