Interleukin‐37 promotes DMBA/TPA skin cancer through SIGIRR‐mediated inhibition of glycolysis in CD103+DC cells
Abstract Interleukin 37 (IL‐37), a member of the IL‐1 family, is considered a suppressor of innate and adaptive immunity and, hence is a regulator of tumor immunity. However, the specific molecular mechanism and role of IL‐37 in skin cancer remain unclear. Here, we report that IL‐37b‐transgenic mice...
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.229 |
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| author | Fan‐lian Zeng Xiao‐yan Wang Ya‐wen Hu Zhen Wang Ya Li Jing Hu Jia‐dong Yu Pei Zhou Xiu Teng Hong Zhou Hua‐ping Zheng Fu‐lei Zhao Lin‐na Gu Cheng‐cheng Yue Shu‐wen Chen Juan Cheng Yan Hao Qi‐xiang Zhao Chen Zhang Song Zou Zhong‐lan Hu Xiao‐qiong Wei Xiao Liu Guo‐lin Li Nong‐yu Huang Wen‐ling Wu Yi‐fan Zhou Wei Li Kaijun Cui Jiong Li |
| author_facet | Fan‐lian Zeng Xiao‐yan Wang Ya‐wen Hu Zhen Wang Ya Li Jing Hu Jia‐dong Yu Pei Zhou Xiu Teng Hong Zhou Hua‐ping Zheng Fu‐lei Zhao Lin‐na Gu Cheng‐cheng Yue Shu‐wen Chen Juan Cheng Yan Hao Qi‐xiang Zhao Chen Zhang Song Zou Zhong‐lan Hu Xiao‐qiong Wei Xiao Liu Guo‐lin Li Nong‐yu Huang Wen‐ling Wu Yi‐fan Zhou Wei Li Kaijun Cui Jiong Li |
| author_sort | Fan‐lian Zeng |
| collection | DOAJ |
| description | Abstract Interleukin 37 (IL‐37), a member of the IL‐1 family, is considered a suppressor of innate and adaptive immunity and, hence is a regulator of tumor immunity. However, the specific molecular mechanism and role of IL‐37 in skin cancer remain unclear. Here, we report that IL‐37b‐transgenic mice (IL‐37tg) treated with the carcinogenic 7,12‐dimethylbenzoanthracene (DMBA)/12‐o‐tetradecylphorbol‐13‐acetate (TPA) exhibited enhanced skin cancer and increased tumor burden in the skin by inhibiting the function of CD103+ dendritic cells (DCs). Notably, IL‐37 induced rapid phosphorylation of adenosine 5‘‐monophosphate (AMP)‐activated protein kinase (AMPK), and via single immunoglobulin IL‐1‐related receptor (SIGIRR), inhibited the long‐term Akt activation. Specifically, by affecting the SIGIRR‐AMPK‐Akt signaling axis, which is related to the regulation of glycolysis in CD103+DCs, IL‐37 inhibited their anti‐tumor function. Our results show that a marked correlation between the CD103+DC signature (IRF8, FMS‐like tyrosine kinase 3 ligand, CLEC9A, CLNK, XCR1, BATF3, and ZBTB46) and chemokines C‐X‐C motif chemokine ligand 9, CXCL10, and CD8A in a mouse model with DMBA/TPA‐induced skin cancer. In a word, our results highlight that IL‐37 as an inhibitor of tumor immune surveillance through modulating CD103+DCs and establishing an important link between metabolism and immunity as a therapeutic target for skin cancer. |
| format | Article |
| id | doaj-art-1535f09d5e044e6890b874393ac6084f |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-1535f09d5e044e6890b874393ac6084f2025-01-24T05:36:29ZengWileyMedComm2688-26632023-04-0142n/an/a10.1002/mco2.229Interleukin‐37 promotes DMBA/TPA skin cancer through SIGIRR‐mediated inhibition of glycolysis in CD103+DC cellsFan‐lian Zeng0Xiao‐yan Wang1Ya‐wen Hu2Zhen Wang3Ya Li4Jing Hu5Jia‐dong Yu6Pei Zhou7Xiu Teng8Hong Zhou9Hua‐ping Zheng10Fu‐lei Zhao11Lin‐na Gu12Cheng‐cheng Yue13Shu‐wen Chen14Juan Cheng15Yan Hao16Qi‐xiang Zhao17Chen Zhang18Song Zou19Zhong‐lan Hu20Xiao‐qiong Wei21Xiao Liu22Guo‐lin Li23Nong‐yu Huang24Wen‐ling Wu25Yi‐fan Zhou26Wei Li27Kaijun Cui28Jiong Li29State Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaLaboratory of Human Disease and Immunotherapies West China Hospital Sichuan University Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaDepartment of Cardiology West China Hospital Sichuan University Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaDepartment of Dermatovenereology West China Hospital Sichuan University Chengdu ChinaDepartment of Cardiology West China Hospital Sichuan University Chengdu ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu ChinaAbstract Interleukin 37 (IL‐37), a member of the IL‐1 family, is considered a suppressor of innate and adaptive immunity and, hence is a regulator of tumor immunity. However, the specific molecular mechanism and role of IL‐37 in skin cancer remain unclear. Here, we report that IL‐37b‐transgenic mice (IL‐37tg) treated with the carcinogenic 7,12‐dimethylbenzoanthracene (DMBA)/12‐o‐tetradecylphorbol‐13‐acetate (TPA) exhibited enhanced skin cancer and increased tumor burden in the skin by inhibiting the function of CD103+ dendritic cells (DCs). Notably, IL‐37 induced rapid phosphorylation of adenosine 5‘‐monophosphate (AMP)‐activated protein kinase (AMPK), and via single immunoglobulin IL‐1‐related receptor (SIGIRR), inhibited the long‐term Akt activation. Specifically, by affecting the SIGIRR‐AMPK‐Akt signaling axis, which is related to the regulation of glycolysis in CD103+DCs, IL‐37 inhibited their anti‐tumor function. Our results show that a marked correlation between the CD103+DC signature (IRF8, FMS‐like tyrosine kinase 3 ligand, CLEC9A, CLNK, XCR1, BATF3, and ZBTB46) and chemokines C‐X‐C motif chemokine ligand 9, CXCL10, and CD8A in a mouse model with DMBA/TPA‐induced skin cancer. In a word, our results highlight that IL‐37 as an inhibitor of tumor immune surveillance through modulating CD103+DCs and establishing an important link between metabolism and immunity as a therapeutic target for skin cancer.https://doi.org/10.1002/mco2.229CD103+DCsglycolysisinterleukin‐37SIGIRRskin cancer |
| spellingShingle | Fan‐lian Zeng Xiao‐yan Wang Ya‐wen Hu Zhen Wang Ya Li Jing Hu Jia‐dong Yu Pei Zhou Xiu Teng Hong Zhou Hua‐ping Zheng Fu‐lei Zhao Lin‐na Gu Cheng‐cheng Yue Shu‐wen Chen Juan Cheng Yan Hao Qi‐xiang Zhao Chen Zhang Song Zou Zhong‐lan Hu Xiao‐qiong Wei Xiao Liu Guo‐lin Li Nong‐yu Huang Wen‐ling Wu Yi‐fan Zhou Wei Li Kaijun Cui Jiong Li Interleukin‐37 promotes DMBA/TPA skin cancer through SIGIRR‐mediated inhibition of glycolysis in CD103+DC cells MedComm CD103+DCs glycolysis interleukin‐37 SIGIRR skin cancer |
| title | Interleukin‐37 promotes DMBA/TPA skin cancer through SIGIRR‐mediated inhibition of glycolysis in CD103+DC cells |
| title_full | Interleukin‐37 promotes DMBA/TPA skin cancer through SIGIRR‐mediated inhibition of glycolysis in CD103+DC cells |
| title_fullStr | Interleukin‐37 promotes DMBA/TPA skin cancer through SIGIRR‐mediated inhibition of glycolysis in CD103+DC cells |
| title_full_unstemmed | Interleukin‐37 promotes DMBA/TPA skin cancer through SIGIRR‐mediated inhibition of glycolysis in CD103+DC cells |
| title_short | Interleukin‐37 promotes DMBA/TPA skin cancer through SIGIRR‐mediated inhibition of glycolysis in CD103+DC cells |
| title_sort | interleukin 37 promotes dmba tpa skin cancer through sigirr mediated inhibition of glycolysis in cd103 dc cells |
| topic | CD103+DCs glycolysis interleukin‐37 SIGIRR skin cancer |
| url | https://doi.org/10.1002/mco2.229 |
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