BACKGROUND After peripheral nerve transection, facial motoneuron (FMN) survival depends on an intact CD4+ T cell population and a central source of interleukin-10 (IL-10). However, it has not been determined previously whether CD4+ T cells participate in the central neuroprotective IL-10 cascade after facial nerve axotomy (FNA). METHODS Immunohistochemical labeling of CD4+ T cells, pontine vasculature, and central microglia was used to determine whether CD4+ T cells cross the blood-brain barrier and enter the facial motor nucleus (FMNuc) after FNA. The importance of IL-10 signaling in CD4+ T cells was assessed by performing adoptive transfer of IL-10 receptor beta (IL-10RB)-deficient CD4+ T cells into immunodeficient mice prior to injury. Histology and qPCR were utilized to determine the impact of IL-10RB-deficient T cells on FMN survival and central gene expression after FNA. Flow cytometry was used to determine whether IL-10 signaling in T cells was necessary for their differentiation into neuroprotective subsets. RESULTS CD4+ T cells were capable of crossing the blood-brain barrier and associating with reactive microglial nodules in the axotomized FMNuc. Full induction of central IL-10R gene expression after FNA was dependent on CD4+ T cells, regardless of their own IL-10R signaling capability. Surprisingly, CD4+ T cells lacking IL-10RB were incapable of mediating neuroprotection after axotomy and promoted increased central expression of genes associated with microglial activation, antigen presentation, T cell co-stimulation, and complement deposition. There was reduced differentiation of IL-10RB-deficient CD4+ T cells into regulatory CD4+ T cells in vitro. CONCLUSIONS These findings support the interdependence of IL-10- and CD4+ T cell-mediated mechanisms of neuroprotection after axotomy. CD4+ T cells may potentiate central responsiveness to IL-10, while IL-10 signaling within CD4+ T cells is necessary for their ability to rescue axotomized motoneuron survival. We propose that loss of IL-10 signaling in CD4+ T cells promotes non-neuroprotective autoimmunity after FNA.

中文翻译：

---

IL-10受体的CD4 + T细胞表达对于轴突切开术后面部运动神经元存活是必需的。

背景技术周围神经横断后，面部运动神经元（FMN）的存活取决于完整的CD4 + T细胞群体和白介素10（IL-10）的主要来源。但是，先前尚未确定在面神经轴突切开术（FNA）后CD4 + T细胞是否参与中枢神经保护性IL-10级联反应。方法采用CD4 + T细胞，桥脑血管和中央小胶质细胞的免疫组织化学标记，确定FNA后CD4 + T细胞是否穿过血脑屏障并进入面部运动核（FMNuc）。通过在损伤前将IL-10受体β（IL-10RB）缺陷型CD4 + T细胞过继转移至免疫缺陷型小鼠中，评估了CD4 + T细胞中IL-10信号传导的重要性。组织学和qPCR用于确定IL-10RB缺陷型T细胞对FNA后FMN存活和中心基因表达的影响。流式细胞仪用于确定T细胞中的IL-10信号转导为分化成神经保护性亚型是否必要。结果CD4 + T细胞能够穿过血脑屏障，并与切成线的FMNuc中的反应性小胶质细胞结节相关。FNA后中央IL-10R基因表达的完全诱导取决于CD4 + T细胞，无论其自身的IL-10R信号传导能力如何。出人意料的是，缺乏IL-10RB的CD4 + T细胞在轴突切开后无法介导神经保护作用，并促进与小胶质细胞活化，抗原呈递，T细胞共刺激和补体沉积有关的基因的中央表达增加。体外，IL-10RB缺陷型CD4 + T细胞向调节性CD4 + T细胞的分化降低。结论这些发现支持了轴突切开术后IL-10-和CD4 + T细胞介导的神经保护机制的相互依赖性。CD4 + T细胞可能增强对IL-10的中枢反应能力，而CD4 + T细胞内的IL-10信号传导对于挽救轴突化的运动神经元存活至关重要。我们建议，FNA后，CD4 + T细胞中IL-10信号的丢失会促进非神经保护性自身免疫。而CD4 + T细胞内的IL-10信号转导对于挽救轴突化的运动神经元存活至关重要。我们建议，FNA后，CD4 + T细胞中IL-10信号的丢失会促进非神经保护性自身免疫。而CD4 + T细胞内的IL-10信号转导对于挽救轴突化的运动神经元存活至关重要。我们建议，FNA后，CD4 + T细胞中IL-10信号的丢失会促进非神经保护性自身免疫。