T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is an important immune checkpoint molecule initially identified as a marker of IFN-γ–producing CD4 + and CD8 + T cells. Since then, our understanding of its role in immune responses has significantly expanded. Here, we review emerging evidence demonstrating unexpected roles for TIM-3 as a key regulator of myeloid cell function, in addition to recent work establishing TIM-3 as a delineator of terminal T cell exhaustion, thereby positioning TIM-3 at the interface between fatigued immune responses and reinvigoration. We share our perspective on the antagonism between TIM-3 and T cell stemness, discussing both cell-intrinsic and cell-extrinsic mechanisms underlying this relationship. Looking forward, we discuss approaches to decipher the underlying mechanisms by which TIM-3 regulates stemness, which has remarkable potential for the treatment of cancer, autoimmunity, and autoinflammation.

中文翻译：

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超越 T 细胞耗竭：TIM-3 对骨髓细胞的调节

T 细胞免疫球蛋白和粘蛋白结构域蛋白 3 (TIM-3) 是一种重要的免疫检查点分子，最初被确定为产生 IFN-γ 的 CD4 的标记物+和CD8+T细胞。从那时起，我们对其在免疫反应中的作用的了解显着扩大。在这里，我们回顾了新出现的证据，证明 TIM-3 作为骨髓细胞功能的关键调节剂发挥着意想不到的作用，此外最近的工作将 TIM-3 确定为终末 T 细胞耗竭的描述器，从而将 TIM-3 定位于疲劳和疲劳之间的界面。免疫反应和恢复活力。我们分享了对 TIM-3 和 T 细胞干性之间拮抗作用的看法，讨论了这种关系背后的细胞内在和细胞外在机制。展望未来，我们将讨论破译 TIM-3 调节干性的潜在机制的方法，该机制在治疗癌症、自身免疫和自身炎症方面具有巨大的潜力。