Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Mexico City, Mexico.
Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico.
J Immunol Res. 2023 Oct 26;2023:3577334. doi: 10.1155/2023/3577334. eCollection 2023.
T-cell Immunoglobulin and Mucin Domain 3 (TIM-3) is an immune checkpoint receptor known to regulate T-cell activation and has been targeted for immunotherapy in cancer and other diseases. However, its expression and function in other cell types, such as macrophages, are poorly understood. This study investigated TIM-3 expression in human macrophages polarized to M1 (stimulated with IFN- and LPS) and M2 (stimulated with IL-4 and IL-13) phenotypes using an in vitro model. Our results show that M1 macrophages have a lower frequency of TIM-3+ cells compared to M2 macrophages at 48 and 72 hr poststimulation. Additionally, we observed differential levels of soluble ADAM 10, an enzyme responsible for TIM-3 release, in the supernatants of M1 and M2 macrophages at 72 hr. We also found that the TIM-3 intracellular tail might associate with lymphocyte-specific protein 1 (LSP-1), a protein implicated in cell motility and podosome formation. These findings enhance our understanding of TIM-3 function in myeloid cells such as macrophages and may inform the development of immunotherapies with reduced immune-related adverse effects.
T 细胞免疫球蛋白和粘蛋白结构域 3（TIM-3）是一种免疫检查点受体，已知其可调节 T 细胞的激活，已被作为癌症和其他疾病的免疫治疗靶点。然而，其在其他细胞类型（如巨噬细胞）中的表达和功能仍知之甚少。本研究通过体外模型，研究了 TIM-3 在极化至 M1（用 IFN- 和 LPS 刺激）和 M2（用 IL-4 和 IL-13 刺激）表型的人巨噬细胞中的表达。我们的结果表明，与 M2 巨噬细胞相比，刺激后 48 和 72 小时，M1 巨噬细胞中 TIM-3+细胞的频率较低。此外，我们还观察到，在 M1 和 M2 巨噬细胞的上清液中，在 72 小时时，可溶性 ADAM 10（一种负责 TIM-3 释放的酶）的水平存在差异。我们还发现，TIM-3 细胞内尾部可能与淋巴细胞特异性蛋白 1（LSP-1）结合，LSP-1 是一种与细胞迁移和足突形成有关的蛋白。这些发现提高了我们对 TIM-3 在巨噬细胞等髓样细胞中的功能的理解，可能为开发具有减少免疫相关不良反应的免疫疗法提供信息。
