脊髓损伤 (SCI) 是一种毁灭性的疾病，全球每年有 250,000 至 500,000 例新病例。呼吸道感染，例如肺炎和流感是 SCI 后死亡的主要原因。不幸的是，人们对神经免疫通讯的改变如何影响个体的感染结果知之甚少。在人类和啮齿类动物中，SCI 会导致脊髓交感反射 (SSR) 回路发生适应不良变化，而这对于交感神经功能至关重要。免疫功能受损的原因可能与有害的神经炎症有关，这种炎症不利于神经元的稳态功能、异常的可塑性和过度兴奋的回路。可溶性肿瘤坏死因子 (sTNF) 是一种促炎细胞因子，SCI 后中枢神经系统中的浓度升高，并在损伤后数月内保持升高状态。通过药理学减弱 SCI 后中枢神经系统中的 sTNF，我们能够证明免疫功能得到改善。此外，当我们研究可能参与神经免疫通讯改变的特定细胞群时，我们发现兴奋性 IN 上过度的 TNFR1 活性会促进免疫功能障碍。此外，这一观察结果在 VGluT2 IN 中依赖于 NF-kβ。我们的数据是中枢神经系统内靶点 TNFR1 的第一份报告，该靶点在 T9-SCI 后导致 SCI 诱导的免疫功能障碍，是未来治疗的潜在途径。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Spinal cord injury (SCI) is a devastating condition with 250,000 to 500,000 new cases globally each year. Respiratory infections, e.g., pneumonia and influenza are the leading cause of death after SCI. Unfortunately, there is a poor understanding of how altered neuro-immune communication impacts an individual's outcome to infection. In humans and rodents, SCI leads to maladaptive changes in the spinal-sympathetic reflex (SSR) circuit which is crucial to sympathetic function. The cause of the impaired immune function may be related to harmful neuroinflammation which is detrimental to homeostatic neuronal function, aberrant plasticity, and hyperexcitable circuits. Soluble tumor necrosis factor (sTNF) is a pro-inflammatory cytokine that is elevated in the CNS after SCI and remains elevated for several months after injury. By pharmacologically attenuating sTNF in the CNS after SCI we were able to demonstrate improved immune function. Furthermore, when we investigated the specific cellular population which may be involved in altered neuro-immune communication we reported that excessive TNFR1 activity on excitatory INs promotes immune dysfunction. Furthermore, this observation is NF-kβ dependent in VGluT2 + INs. Our data is the first report of a target within the CNS, TNFR1, that contributes to SCI-induced immune dysfunction after T9-SCI and is a potential avenue for future therapeutics.Copyright © 2024 Elsevier Inc. All rights reserved.