Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, United States.
Department of Anaesthesia and Department of Immunology, Harvard Medical School., Boston, MA, United States.
Front Immunol. 2022 Feb 1;13:819224. doi: 10.3389/fimmu.2022.819224. eCollection 2022.
Due to the plasticity of IL-17-producing CD4 T cells (Th17 cells), a long-standing challenge in studying Th17-driven autoimmune is the lack of specific surface marker to identify the pathogenic Th17 cells . Recently, we discovered that pathogenic CD4 T cells were CXCR6 positive in experimental autoimmune encephalomyelitis (EAE), a commonly used Th17-driven autoimmune model. Herein, we further revealed that peripheral CXCR6CD4 T cells contain a functionally distinct subpopulation, which is CCR6 positive and enriched for conventional Th17 molecules (IL-23R and RORγt) and cytotoxic signatures. Additionally, spinal cord-infiltrating CD4 T cells were highly cytotoxic by expressing Granzyme(s) along with IFNγ and GM-CSF. Collectively, this study suggested that peripheral CCR6CXCR6CD4 T cells were Th17 cells with cytotoxic property in EAE model, and highlighted the cytotoxic granzymes for EAE pathology.
由于产生白细胞介素-17 的 CD4 T 细胞（Th17 细胞）具有可塑性，因此在研究 Th17 驱动的自身免疫中，长期存在的挑战是缺乏用于鉴定致病性 Th17 细胞的特异性表面标志物。最近，我们发现在实验性自身免疫性脑脊髓炎（EAE）中，一种常用的 Th17 驱动的自身免疫模型中，致病性 CD4 T 细胞为 CXCR6 阳性。在此基础上，我们进一步揭示了外周 CXCR6CD4 T 细胞包含一个功能不同的亚群，该亚群 CCR6 阳性，富含常规 Th17 分子（IL-23R 和 RORγt）和细胞毒性特征。此外，脊髓浸润的 CD4 T 细胞通过表达颗粒酶（s）以及 IFNγ 和 GM-CSF 而具有高细胞毒性。总之，这项研究表明，外周 CCR6CXCR6CD4 T 细胞是 EAE 模型中具有细胞毒性的 Th17 细胞，并强调了细胞毒性颗粒酶在 EAE 发病机制中的作用。
