Wang Yan, Wang Zhaoran, Diao Wenya, Shi Tong, Xu Jiahe, Deng Tiantian, Wen Chaoying, Gu Jienan, Deng Tingting, Wang Sixuan, Xiao Cheng
China-Japan Friendship Clinical Medical College, Beijing University of Chinese Medicine, Beijing, 100029, China.
Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, 100029, China.
Clin Rev Allergy Immunol. 2025 Aug 18;68(1):82. doi: 10.1007/s12016-025-09084-9.
Islet macrophages are considered to be irreplaceable in maintaining the immune microenvironment homeostasis. The M1/M2 imbalance can trigger the initiation of islet autoimmunity and persists throughout the entire process of type 1 diabetes. The identification of macrophage transcriptional clusters and phenotypes by single-cell sequencing has facilitated in-depth studies on the role of macrophages in the pathogenesis of type 1 diabetes. Macrophages exert extensive endocrine and paracrine effects on the islets by secreting various bioactive chemicals, especially exosomes, which facilitate cell-cell communication. Resident islet macrophages directly influence the biological properties of islet tissue. Meanwhile, the interaction between macrophages and islet cells is bidirectional. Cell-cell interactions also closely govern the polarization and activity of macrophages. An imbalance in the transition from M2 to M1 macrophages may lead to inflammation and islet dysfunction. Here, we have discussed the latest research progress on macrophages in the islet immune microenvironment homeostasis, the mechanisms of interactions between macrophages and islet cells in type 1 diabetes, and analyzed the possible clinical consequences. Furthermore, we highlighted emerging technologies for non-invasive detection of macrophages and summarized how therapeutic targeting of macrophages may be beneficial for patients with type 1 diabetes.
胰岛巨噬细胞被认为在维持免疫微环境稳态中不可或缺。M1/M2失衡可引发胰岛自身免疫的起始，并贯穿1型糖尿病的整个过程。通过单细胞测序鉴定巨噬细胞转录簇和表型，有助于深入研究巨噬细胞在1型糖尿病发病机制中的作用。巨噬细胞通过分泌各种生物活性化学物质，尤其是外泌体，对胰岛发挥广泛的内分泌和旁分泌作用，从而促进细胞间通讯。驻留胰岛巨噬细胞直接影响胰岛组织的生物学特性。同时，巨噬细胞与胰岛细胞之间的相互作用是双向的。细胞间相互作用也密切调控巨噬细胞的极化和活性。M2向M1巨噬细胞转变的失衡可能导致炎症和胰岛功能障碍。在此，我们讨论了胰岛免疫微环境稳态中巨噬细胞的最新研究进展、1型糖尿病中巨噬细胞与胰岛细胞相互作用的机制，并分析了可能的临床后果。此外，我们强调了巨噬细胞无创检测的新兴技术，并总结了针对巨噬细胞的治疗靶向对1型糖尿病患者可能的益处。
