| First Author | Chen H | Year | 2024 |
| Journal | Sci Rep | Volume | 14 |
| Issue | 1 | Pages | 31937 |
| PubMed ID | 39738540 | Mgi Jnum | J:360906 |
| Mgi Id | MGI:7798489 | Doi | 10.1038/s41598-024-83447-8 |
| Citation | Chen H, et al. (2024) HDAC3 inhibitors induce drug resistance by promoting IL-17 A production by T cells. Sci Rep 14(1):31937 |
| abstractText | 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-gamma 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. |
