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Targeting a disintegrin and metalloprotease (ADAM) 17-CD122 axis enhances CD8 + T cell effector differentiation and anti-tumor immunity.

التفاصيل البيبلوغرافية
العنوان: Targeting a disintegrin and metalloprotease (ADAM) 17-CD122 axis enhances CD8 + T cell effector differentiation and anti-tumor immunity.
المؤلفون: Sun L; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, 710061, China.; Xi'an Key Laboratory of Immune Related Diseases, Xi'an, Shannxi, 710061, China., Jiao A; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, 710061, China.; Xi'an Key Laboratory of Immune Related Diseases, Xi'an, Shannxi, 710061, China., Liu H; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China., Ding R; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China., Yuan N; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China., Yang B; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China., Zhang C; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China., Jia X; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China., Wang G; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China., Su Y; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, 710061, China.; Xi'an Key Laboratory of Immune Related Diseases, Xi'an, Shannxi, 710061, China., Zhang D; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China., Shi L; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.; Xi'an Key Laboratory of Immune Related Diseases, Xi'an, Shannxi, 710061, China., Sun C; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China. cm.sun@xjtu.edu.cn.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China. cm.sun@xjtu.edu.cn.; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, 710061, China. cm.sun@xjtu.edu.cn.; Xi'an Key Laboratory of Immune Related Diseases, Xi'an, Shannxi, 710061, China. cm.sun@xjtu.edu.cn., Zhang A; Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China. zhangaijun@sdu.edu.cn., Zhang L; National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, 215123, Jiangsu, China. zlj@ism.cams.cn.; Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, 215123, Jiangsu, China. zlj@ism.cams.cn., Zhang B; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China. bj.zhang@mail.xjtu.edu.cn.; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China. bj.zhang@mail.xjtu.edu.cn.; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, 710061, China. bj.zhang@mail.xjtu.edu.cn.; Xi'an Key Laboratory of Immune Related Diseases, Xi'an, Shannxi, 710061, China. bj.zhang@mail.xjtu.edu.cn.
المصدر: Signal transduction and targeted therapy [Signal Transduct Target Ther] 2024 Jun 26; Vol. 9 (1), pp. 152. Date of Electronic Publication: 2024 Jun 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101676423 Publication Model: Electronic Cited Medium: Internet ISSN: 2059-3635 (Electronic) Linking ISSN: 20593635 NLM ISO Abbreviation: Signal Transduct Target Ther Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Publishing Group, [2016]-
مواضيع طبية MeSH: ADAM17 Protein*/genetics , ADAM17 Protein*/immunology , CD8-Positive T-Lymphocytes*/immunology , Cell Differentiation*/immunology , Cell Differentiation*/genetics , Cell Differentiation*/drug effects, Animals ; Mice ; Humans ; Neoplasms/immunology ; Neoplasms/genetics ; Neoplasms/pathology
مستخلص: CD8 + T cell immune responses are regulated by multi-layer networks, while the post-translational regulation remains largely unknown. Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins. Here, by targeting the sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8 + T cells. Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8 + T cells. T cell-specific deletion of ADAM17 led to a dramatic increase in effector CD8 + T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors. Mechanistically, ADAM17 regulated CD8 + T cells through cleavage of membrane CD122. ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8 + T cells. Intriguingly, inhibition of ADAM17 in CD8 + T cells improved the efficacy of chimeric antigen receptor (CAR) T cells in solid tumors. Our findings reveal a critical post-translational regulation in CD8 + T cells, providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 82271792 National Natural Science Foundation of China (National Science Foundation of China); 32200727 National Natural Science Foundation of China (National Science Foundation of China); 82071828 National Natural Science Foundation of China (National Science Foundation of China); 2017JM8148 Natural Science Foundation of Shaanxi Province (Shaanxi Province Natural Science Foundation)
المشرفين على المادة: EC 3.4.24.86 (ADAM17 Protein)
EC 3.4.24.86 (ADAM17 protein, human)
EC 3.4.24.86 (Adam17 protein, mouse)
تواريخ الأحداث: Date Created: 20240625 Date Completed: 20240625 Latest Revision: 20240712
رمز التحديث: 20240712
مُعرف محوري في PubMed: PMC11199508
DOI: 10.1038/s41392-024-01873-6
PMID: 38918390
قاعدة البيانات: MEDLINE
الوصف
تدمد:2059-3635
DOI:10.1038/s41392-024-01873-6