基因Cblb,也称为Casitas B淋巴瘤-b,是一种重要的E3泛素连接酶。E3泛素连接酶是泛素化途径中的关键酶,负责将泛素分子连接到底物蛋白上,从而标记这些蛋白进行降解或调节其功能。Cblb在多种细胞类型中发挥重要作用,包括免疫细胞、心脏细胞和神经细胞等。
Cblb在免疫系统中具有重要的调节作用。它可以抑制T细胞和NK细胞的激活,从而抑制免疫反应。此外,Cblb还可以调节B细胞的发育和功能。研究表明,Cblb的缺陷会导致T细胞和NK细胞的过度激活,以及B细胞的发育异常,从而增加自身免疫性疾病的风险[2,4,7]。
Cblb在肿瘤免疫治疗中也具有重要的应用价值。Cblb可以抑制肿瘤微环境中的免疫抑制,从而增强免疫治疗的效果。研究表明,Cblb的抑制剂可以增强T细胞和NK细胞的功能,促进肿瘤的消退[1,3]。此外,Cblb的抑制剂还可以增强CAR-T细胞的治疗效果,克服CAR-T细胞在肿瘤微环境中的功能障碍[3]。
除了在免疫系统中的作用,Cblb还在其他疾病中发挥重要作用。例如,Cblb的缺陷会导致维生素依赖性甲基丙二酸尿症,这是一种代谢性疾病[5]。此外,Cblb的表达异常还与急性心肌梗死的发生发展相关[6]。
综上所述,基因Cblb在多种生物学过程中发挥重要作用,包括免疫调节、肿瘤免疫治疗、代谢性疾病和心血管疾病等。Cblb的研究有助于深入理解其生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Augustin, Ryan C, Bao, Riyue, Luke, Jason J. . Targeting Cbl-b in cancer immunotherapy. In Journal for immunotherapy of cancer, 11, . doi:10.1136/jitc-2022-006007. https://pubmed.ncbi.nlm.nih.gov/36750253/
2. Yokoi, Norihide, Komeda, Kajuro, Wang, He-Yao, Serikawa, Tadao, Seino, Susumu. 2002. Cblb is a major susceptibility gene for rat type 1 diabetes mellitus. In Nature genetics, 31, 391-4. doi:. https://pubmed.ncbi.nlm.nih.gov/12118252/
3. Kumar, Jitendra, Kumar, Ritesh, Kumar Singh, Amir, Davila, Marco L, Venuprasad, K. . Deletion of Cbl-b inhibits CD8+ T-cell exhaustion and promotes CAR T-cell function. In Journal for immunotherapy of cancer, 9, . doi:10.1136/jitc-2020-001688. https://pubmed.ncbi.nlm.nih.gov/33462140/
4. Matsuda, Junko, Yokota, Ichiro. 2008. cblb Gene Analysis in Japanese Type 1 Diabetes with Younger Age of Onset. In Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 17, 31-8. doi:10.1297/cpe.17.31. https://pubmed.ncbi.nlm.nih.gov/24790360/
5. Dobson, C Melissa, Wai, Timothy, Leclerc, Daniel, Rosenblatt, David S, Gravel, Roy A. . Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria. In Human molecular genetics, 11, 3361-9. doi:. https://pubmed.ncbi.nlm.nih.gov/12471062/
6. You, Hongjun, Chang, Fengjun, Chen, Haichao, Wang, Yi, Han, Wenqi. 2024. Exploring the role of CBLB in acute myocardial infarction: transcriptomic, microbiomic, and metabolomic analyses. In Journal of translational medicine, 22, 654. doi:10.1186/s12967-024-05425-y. https://pubmed.ncbi.nlm.nih.gov/39004726/
7. Song, Jing, Anderson, Warren, Hu, Alex, Rawlings, David J, Buckner, Jane H. 2022. CBLB Deficiency in Human CD4+ T Cells Results in Resistance to T Regulatory Suppression through Multiple Mechanisms. In Journal of immunology (Baltimore, Md. : 1950), 209, 1260-1271. doi:10.4049/jimmunol.2200219. https://pubmed.ncbi.nlm.nih.gov/36165179/