机构：[1]Department of Health Management Centre & Institute of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610000, China四川省人民医院[2]Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammation Biology, State Key Laboratory of Experimental Hematology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China[3]Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China河南省肿瘤医院[4]University of Electronic Science and Technology of China, Chengdu 611731, China[5]Department of Critical Care Medicine, Department of Anesthesiology, Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China[6]Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China河南省肿瘤医院[7]The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, Tianjin Medical University, Tianjin 300070, China[8]State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China[9]Tianjin Institutes of Health Science, Tianjin 301600, China
Riboflavin kinase (RFK) is essential in riboflavin metabolism, converting riboflavin to flavin mononucleotide (FMN), which is further processed to flavin adenine dinucleotide (FAD). While RFK enhances macrophage phagocytosis of Listeria monocytogenes, its role in macrophage polarization is not well understood. Our study reveals that RFK deficiency impairs M(IFN-gamma) and promotes M(IL-4) polarization, both in vitro and in vivo. Mechanistically, RFK interacts with inducible nitric oxide (NO) synthase (iNOS), which requires FMN and FAD as cofactors for activation, leading to increased NO production that alters energy metabolism by inhibiting the tricarboxylic acid cycle and mitochondrial electron transport chain. Exogenous FAD reverses the metabolic and polarization changes caused by RFK deficiency. Furthermore, bone marrow adoptive transfer from highriboflavin-fed mice into wild-type tumor-bearing mice reprograms tumor-associated macrophage polarization and inhibits tumor growth. These results suggest that targeting RFK-iNOS or modulating riboflavin metabolism could be potential therapies for macrophage-related immune diseases.
基金：
Postdoctoral Fellowship Program of CPSF [GZB20240116]; National Natural Science Foundation of China [32471218, 82273088, 82073051, 82273217]; Tianjin Municipal Natural Science Foundation of China [22JCQNJC00040]
第一作者机构：[1]Department of Health Management Centre & Institute of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610000, China[2]Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammation Biology, State Key Laboratory of Experimental Hematology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Health Management Centre & Institute of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610000, China[2]Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammation Biology, State Key Laboratory of Experimental Hematology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China[8]State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China[9]Tianjin Institutes of Health Science, Tianjin 301600, China
推荐引用方式(GB/T 7714)：
Shan Xiao,Ji Zemin,Wang Baochen,et al.Riboflavin kinase binds and activates inducible nitric oxide synthase to reprogram macrophage polarization[J].REDOX BIOLOGY.2024,78:doi:10.1016/j.redox.2024.103413.
APA：
Shan, Xiao,Ji, Zemin,Wang, Baochen,Zhang, Yanan,Dong, Hongyuan...&Yu, Qiujing.(2024).Riboflavin kinase binds and activates inducible nitric oxide synthase to reprogram macrophage polarization.REDOX BIOLOGY,78,
MLA：
Shan, Xiao,et al."Riboflavin kinase binds and activates inducible nitric oxide synthase to reprogram macrophage polarization".REDOX BIOLOGY 78.(2024)
生物学