HDAC3 inhibitors induce drug resistance by promoting IL-17 A production by T cells
Abstract HDAC3 has been demonstrated to play a crucial role in the progression of various tumors and the differentiation and development of T cells. However, its impact on peripheral T cells in the development of murine lung cancer remains unclear. In this experiment, a subcutaneous lung tumor model...
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| Format: | Article |
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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-83447-8 |
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| author | Hao Chen Anqi Qin Fan Xu Shuai Guo Ge Zhang Aihong Zhang WenTing Li Feng Tian Quanhui Zheng |
| author_facet | Hao Chen Anqi Qin Fan Xu Shuai Guo Ge Zhang Aihong Zhang WenTing Li Feng Tian Quanhui Zheng |
| author_sort | Hao Chen |
| collection | DOAJ |
| description | Abstract HDAC3 has been demonstrated to play a crucial role in the progression of various tumors and the differentiation and development of T cells. However, its impact on peripheral T cells in the development of murine lung cancer remains unclear. In this experiment, a subcutaneous lung tumor model was established in C57BL/6 mice, and tumor-bearing mice were treated with the specific inhibitor of HDAC3, RGFP966, at different doses to observe changes in tumor size. Additionally, a lung tumor model was established using hdac3 fl/fl cd4cre +/+ mice to investigate its mechanism. Mice injected with 10 mg/kg RGFP966 had the smallest tumor volume, while those injected with 30 mg/kg RGFP966 had the largest tumors. Flow cytometry analysis revealed that the expression of HDAC3 in splenic T cells was reduced in all groups of mice, while IFN-γ and IL-17 A were increased. Moreover, the expression of granzyme B and perforin in splenic CD8+ T cells was increased in all groups of mice. Compared to the use of 30 mg/kg RGFP966 alone, the combination with anti-IL-17 A mAb reduced the infiltration of Neutrophils and exhausted T cells in mouse tumors, thereby impeding tumor development. These findings demonstrate that the use of RGFP966 or T cell-specific loss of hdac3 promotes the expression of IL-17 A in splenic T cells, leading to tumor resistance and providing insights for clinical treatment. |
| format | Article |
| id | doaj-art-ae554269ffe9470f9052d89874abdf57 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
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| spelling | doaj-art-ae554269ffe9470f9052d89874abdf572025-01-05T12:24:10ZengNature PortfolioScientific Reports2045-23222024-12-011411910.1038/s41598-024-83447-8HDAC3 inhibitors induce drug resistance by promoting IL-17 A production by T cellsHao Chen0Anqi Qin1Fan Xu2Shuai Guo3Ge Zhang4Aihong Zhang5WenTing Li6Feng Tian7Quanhui Zheng8Hebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and TechnologyHebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and TechnologyHebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and TechnologyHebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and TechnologySchool of Basic Medical, Xingtai Medical CollegeDepartment of ICU, The Affiliated Hospital of North China University of Science and TechnologyDepartment of Laboratory Animal Science, Health Science Center, Peking UniversityDepartment of Laboratory Animal Science, Health Science Center, Peking UniversityHebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and TechnologyAbstract HDAC3 has been demonstrated to play a crucial role in the progression of various tumors and the differentiation and development of T cells. However, its impact on peripheral T cells in the development of murine lung cancer remains unclear. In this experiment, a subcutaneous lung tumor model was established in C57BL/6 mice, and tumor-bearing mice were treated with the specific inhibitor of HDAC3, RGFP966, at different doses to observe changes in tumor size. Additionally, a lung tumor model was established using hdac3 fl/fl cd4cre +/+ mice to investigate its mechanism. Mice injected with 10 mg/kg RGFP966 had the smallest tumor volume, while those injected with 30 mg/kg RGFP966 had the largest tumors. Flow cytometry analysis revealed that the expression of HDAC3 in splenic T cells was reduced in all groups of mice, while IFN-γ and IL-17 A were increased. Moreover, the expression of granzyme B and perforin in splenic CD8+ T cells was increased in all groups of mice. Compared to the use of 30 mg/kg RGFP966 alone, the combination with anti-IL-17 A mAb reduced the infiltration of Neutrophils and exhausted T cells in mouse tumors, thereby impeding tumor development. These findings demonstrate that the use of RGFP966 or T cell-specific loss of hdac3 promotes the expression of IL-17 A in splenic T cells, leading to tumor resistance and providing insights for clinical treatment.https://doi.org/10.1038/s41598-024-83447-8 |
| spellingShingle | Hao Chen Anqi Qin Fan Xu Shuai Guo Ge Zhang Aihong Zhang WenTing Li Feng Tian Quanhui Zheng HDAC3 inhibitors induce drug resistance by promoting IL-17 A production by T cells Scientific Reports |
| title | HDAC3 inhibitors induce drug resistance by promoting IL-17 A production by T cells |
| title_full | HDAC3 inhibitors induce drug resistance by promoting IL-17 A production by T cells |
| title_fullStr | HDAC3 inhibitors induce drug resistance by promoting IL-17 A production by T cells |
| title_full_unstemmed | HDAC3 inhibitors induce drug resistance by promoting IL-17 A production by T cells |
| title_short | HDAC3 inhibitors induce drug resistance by promoting IL-17 A production by T cells |
| title_sort | hdac3 inhibitors induce drug resistance by promoting il 17 a production by t cells |
| url | https://doi.org/10.1038/s41598-024-83447-8 |
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