Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA; Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, 11217, Taiwan; Faculty of Medicine, National Yang Ming Chiao Tung University, Hsinchu, 30010, Taiwan.
Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA; Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
J Autoimmun. 2022 May;129:102816. doi: 10.1016/j.jaut.2022.102816. Epub 2022 Apr 5.
Effector Th17 cells, including IFN-γIL-17 (eTh17) and IFN-γIL-17 (eTh17/1) subsets, play critical pathogenic functions in the induction of autoimmunity. As acute inflammation subsides, a small proportion of the effectors survive and convert to memory Th17 cells (mTh17), which sustain chronic inflammation in autoimmune diseases. Herein, we investigated the differential contributions of eTh17 versus eTh17/1 to the memory pool using an experimental model of ocular autoimmune disease. Our results show that adoptive transfer of Tbx21 CD4 T cells or conditional deletion of Tbx21 in Th17 cells leads to diminished eTh17/1 in acute phase and functionally compromised mTh17 in chronic phase. Further, adoptive transfer of disease-specific eTh17/1, but not eTh17, leads to generation of mTh17 and sustained ocular inflammation. Collectively, our data demonstrate that T-bet-dependent eTh17/1 cells generated during the acute inflammation are the principal effector precursors of pathogenic mTh17 cells that sustain the chronicity of autoimmune inflammation.
效应性 Th17 细胞，包括 IFN-γIL-17（eTh17）和 IFN-γIL-17（eTh17/1）亚群，在自身免疫的诱导中发挥关键的致病作用。随着急性炎症的消退，一小部分效应物存活并转化为记忆性 Th17 细胞（mTh17），在自身免疫性疾病中维持慢性炎症。在此，我们使用眼部自身免疫性疾病的实验模型研究了 eTh17 与 eTh17/1 对记忆池的不同贡献。我们的结果表明，Tbx21 CD4 T 细胞的过继转移或 Th17 细胞中 Tbx21 的条件性缺失导致急性期 eTh17/1 减少，慢性期功能受损的 mTh17 增加。此外，疾病特异性 eTh17/1 的过继转移而不是 eTh17 的过继转移导致 mTh17 的产生和持续的眼部炎症。总之，我们的数据表明，在急性炎症期间产生的 T-bet 依赖性 eTh17/1 细胞是致病性 mTh17 细胞的主要效应前体细胞，维持着自身免疫炎症的慢性。
