Abstract:
Previously we reported that a recombinant HSV-1 expressing murine IL-2 (HSV-IL-2) causes CNS demyelination in different strains of mice and in a T cell-dependent manner. Since TH17 cells have been implicated in CNS pathology, in the present study, we looked into the effects of IL-17A-/- and three of its receptors on HSV-IL-2-induced CNS demyelination. IL-17A-/- mice did not develop CNS demyelination, while IL-17RA-/-, IL-17RC-/-, IL-17RD-/- and IL-17RA-/-RC-/- mice developed CNS demyelination. Adoptive transfer of T cells from wild-type (WT) mice to IL-17A-/- mice or T cells from IL-17A-/- mice to Rag-/- mice induced CNS demyelination in infected mice. Adoptive T cell experiments suggest that both T cells and non-T cells expressing IL-17A contribute to HSV-IL-2-induced CNS demyelination with no difference in the severity of demyelination between the two groups of IL-17A producing cells. IL-6, IL-10, or TGFβ did not contribute to CNS demyelination in infected mice. Transcriptome analysis between IL-17A-/- brain and spinal cord of infected mice with and without T cell transfer from WT mice revealed that \"neuron projection extension involved in neuron projection guidance\" and \"ensheathment of neurons\" pathways were associated with CNS demyelination. Collectively, the results indicate the importance of IL-17A in CNS demyelination and the possible involvement of more than three of IL-17 receptors in CNS demyelination.
摘要:
以前,我们报道了表达鼠IL-2(HSV-IL-2)的重组HSV-1在不同品系小鼠中以T细胞依赖性方式引起CNS脱髓鞘。由于TH17细胞与CNS病理有关,在本研究中,我们研究了IL-17A-/-及其三种受体对HSV-IL-2诱导的CNS脱髓鞘的影响。IL-17A-/-小鼠未发生中枢神经系统脱髓鞘,而IL-17RA-/-,IL-17RC-/-,IL-17RD-/-和IL-17RA-/-RC-/-小鼠发生CNS脱髓鞘。T细胞从野生型(WT)小鼠过继转移至IL-17A-/-小鼠或T细胞从IL-17A-/-小鼠过继转移至Rag-/-小鼠在感染小鼠中诱导CNS脱髓鞘。过继性T细胞实验表明,表达IL-17A的T细胞和非T细胞均有助于HSV-IL-2诱导的CNS脱髓鞘,两组产生IL-17A的细胞之间的脱髓鞘严重程度没有差异。IL-6、IL-10或TGFβ不有助于感染小鼠的CNS脱髓鞘。在有和没有WT小鼠T细胞转移的感染小鼠的IL-17A-/-脑和脊髓之间的转录组分析显示,“参与神经元投影引导的神经元投影延伸”和“神经元鞘化”途径与中枢神经系统脱髓鞘有关。总的来说,结果表明IL-17A在CNS脱髓鞘中的重要性以及三种以上IL-17受体可能参与CNS脱髓鞘。