Manganese suppresses the development of oral leukoplakia by activating the immune response

作者：Yujie Shi, Chongying Su, Tingting Ding, Hang Zhao, Ying Wang, Yuan Ren, Lanyan Wu, Qiyue Zhang, Jing Liang, Silu Sun, Jiongke Wang, Jing Li, Xin Zeng · 发表于：Oral Diseases · 年份：2022 · DOI：10.1111/odi.14412 · 被引用次数：7 · 研究领域：interferon and immune responses、Inflammasome and immune disorders、Cancer-related molecular mechanisms research

Abstract Objective Manganese ion (Mn 2+ ) is reported to promote the antitumor immune response by activating the cGAS‐STING pathway, but it is unknown whether Mn 2+ can prevent the malignant transformation of precancerous lesions. The effects of Mn 2+ in treating oral leukoplakia (OLK) were explored in this work. Methods Peripheral blood Mn analysis of the patients was performed using inductively coupled plasma atomic emission spectroscopy (ICP–AES). A coculture model of dendritic cells (DCs)/macrophages, CD8 + T cells, and dysplastic oral keratinocytes (DOKs) was employed to analyze the role and mechanism of Mn 2+ in a simulated OLK immune microenvironment. Western blot, RT–PCR, flow cytometry, enzyme‐linked immunosorbent assay (ELISA), and lactate dehydrogenase (LDH) assays were adopted to detect the mechanism of Mn 2+ in this model. 4‐nitroquinoline oxide (4NQO)‐induced OLK mice were used to assess the role of Mn 2+ in suppressing OLK progression, and a novel Mn 2+ ‐loaded guanosine‐tannic acid hydrogel (G‐TA@Mn 2+ hydrogel) was fabricated and evaluated for its advantages in OLK therapy. Results The content of Mn in patients' peripheral blood was negatively related to the progression of OLK. Mn 2+ promoted the maturation and antigen presentation of DCs and macrophages and enhanced the activation of CD8 + T cells in the coculture model, resulting in effective killing of DOKs. Mechanistic analysis found that Mn 2+ enhanced the anti‐OLK immune response by activating the cGAS‐...