Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, PR China.
Medical Genomics Unit, National Human Genome Research Institute, Bethesda, MD 20814, USA.
Pharmacol Res. 2023 Jun;192:106797. doi: 10.1016/j.phrs.2023.106797. Epub 2023 May 19.
Stroke is a severe and life-threatening disease, necessitating more research on new treatment strategies. Infiltrated T lymphocytes, an essential adaptive immune cell with extensive effector function, are crucially involved in post-stroke inflammation. Immediately after the initiation of the innate immune response triggered by microglia/macrophages, the adaptive immune response associated with T lymphocytes also participates in the complex pathophysiology of stroke and partially informs the outcome of stroke. Preclinical and clinical studies have revealed the conflicting roles of T cells in post-stroke inflammation and as potential therapeutic targets. Therefore, exploring the mechanisms that underlie the adaptive immune response associated with T lymphocytes in stroke is essential. The T-cell receptor (TCR) and its downstream signaling regulate T lymphocyte differentiation and activation. This review comprehensively summarizes the various molecules that regulate TCR signaling and the T-cell response. It covers both the co-stimulatory and co-inhibitory molecules and their roles in stroke. Because immunoregulatory therapies targeting TCR and its mediators have achieved great success in some proliferative diseases, this article also summarizes the advances in therapeutic strategies related to TCR signaling in lymphocytes after stroke, which can facilitate translation.
中风是一种严重且危及生命的疾病,因此需要更多研究新的治疗策略。浸润性 T 淋巴细胞是一种具有广泛效应功能的重要适应性免疫细胞,在中风后的炎症中起着至关重要的作用。在小胶质细胞/巨噬细胞触发的固有免疫反应开始后,与 T 淋巴细胞相关的适应性免疫反应也参与了中风的复杂病理生理学,并在一定程度上影响了中风的结果。临床前和临床研究揭示了 T 细胞在中风后炎症中的矛盾作用及其作为潜在治疗靶点的可能性。因此,探索与 T 淋巴细胞相关的适应性免疫反应的机制至关重要。T 细胞受体 (TCR)及其下游信号转导调节 T 淋巴细胞的分化和激活。本综述全面总结了调节 TCR 信号转导和 T 细胞反应的各种分子。它涵盖了共刺激和共抑制分子及其在中风中的作用。由于针对 TCR 及其介质的免疫调节疗法在一些增殖性疾病中取得了巨大成功,本文还总结了中风后淋巴细胞 TCR 信号相关的治疗策略的进展,这有助于转化。