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Zhang, Wenjie, Liu, Shan, Zhao, Lin, Wang, Juncheng, Liu, Meng, Wang, Fengge, Xu, Yuekang. (1402). LKB1 Positively Regulates Dendritic Cell-induced T Cell Immunity and Suppresses Tumor Development. سامانه مدیریت نشریات علمی, 20(2), 145-158. doi: 10.22034/iji.2023.96163.2412
Wenjie Zhang; Shan Liu; Lin Zhao; Juncheng Wang; Meng Liu; Fengge Wang; Yuekang Xu. "LKB1 Positively Regulates Dendritic Cell-induced T Cell Immunity and Suppresses Tumor Development". سامانه مدیریت نشریات علمی, 20, 2, 1402, 145-158. doi: 10.22034/iji.2023.96163.2412
Zhang, Wenjie, Liu, Shan, Zhao, Lin, Wang, Juncheng, Liu, Meng, Wang, Fengge, Xu, Yuekang. (1402). 'LKB1 Positively Regulates Dendritic Cell-induced T Cell Immunity and Suppresses Tumor Development', سامانه مدیریت نشریات علمی, 20(2), pp. 145-158. doi: 10.22034/iji.2023.96163.2412
Zhang, Wenjie, Liu, Shan, Zhao, Lin, Wang, Juncheng, Liu, Meng, Wang, Fengge, Xu, Yuekang. LKB1 Positively Regulates Dendritic Cell-induced T Cell Immunity and Suppresses Tumor Development. سامانه مدیریت نشریات علمی, 1402; 20(2): 145-158. doi: 10.22034/iji.2023.96163.2412

LKB1 Positively Regulates Dendritic Cell-induced T Cell Immunity and Suppresses Tumor Development

Iranian Journal of Immunology
مقاله 1، دوره 20، شماره 2، شهریور 2023، صفحه 145-158    اصل مقاله (2.37 M)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22034/iji.2023.96163.2412
نویسندگان
Wenjie Zhang؛ Shan Liu؛ Lin Zhao؛ Juncheng Wang؛ Meng Liu؛ Fengge Wang؛ Yuekang Xu*
Anhui Provincial Key Laboratory for Conservation and Exploitation of Biological Resources, School of Life Sciences, Anhui Normal University, Wuhu, China 241000.
چکیده
Background: The functions of dendritic cells (DCs) are influenced by their intracellular metabolism, in which liver kinase B1 (LKB1) plays an important role. However, due to the difficulty in isolating the DCs, the roles of LKB1 in DC maturation and functions in tumor settings have been poorly characterized.
Objective: To investigate the roles of LKB1 in DC functions including phagocytosis and presentation of antigens, activation, T cell differentiation, and ultimately tumor eradication.
Methods: Genetic modification of Lkb1 in the DCs was made by lentiviral transduction, and their impacts on T cell proliferation, differentiation, activity, or B16 melanoma metastasis were examined by flow cytometry, qPCR, or lung tumor nodule counting.
Results: LKB1 did not affect antigen uptake and presentation by the DCs, but facilitated the stimulation of T cell proliferation. Interestingly, following T cell activation, Foxp3-expressing regulatory T cells (Treg) were increased (P=0.0267) or decreased (P=0.0195) in mice injected with Lkb1 knockdown DCs or overexpressing DCs, respectively. Further exploration revealed that LKB1 inhibited OX40L (P=0.0385) and CD86 (P=0.0111) expression, and these co-stimulatory molecules enhanced Treg proliferation, and downregulated immune suppressive cytokine IL-10 (P=0.0315). Moreover, we found that the injection of the DCs with limited LKB1 expression before tumor inoculation could reduce their production of granzyme B (P<0.0001) and perforin (P=0.0042) from CD8+T cells, thereby impairing their cytotoxicity and promoting tumor growth.
Conclusion: Our data suggest that LKB1 can enhance DC-mediated T cell immunity by restraining Treg development and thereby suppressing tumor growth.
کلیدواژه‌ها
Dendritic Cells؛ LKB1؛ Treg؛ Tumor Immunology
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