| First Author | Benjaskulluecha S | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 1 | Pages | 108733 |
| PubMed ID | 38235325 | Mgi Jnum | J:351214 |
| Mgi Id | MGI:7575364 | Doi | 10.1016/j.isci.2023.108733 |
| Citation | Benjaskulluecha S, et al. (2024) O(6)-methylguanine DNA methyltransferase regulates beta-glucan-induced trained immunity of macrophages via farnesoid X receptor and AMPK. iScience 27(1):108733 |
| abstractText | Trained immunity is the heightened state of innate immune memory that enhances immune response resulting in nonspecific protection. Epigenetic changes and metabolic reprogramming are critical steps that regulate trained immunity. In this study, we reported the involvement of O(6)-methylguanine DNA methyltransferase (MGMT), a DNA repair enzyme of lesion induced by alkylating agents, in regulation the trained immunity induced by beta-glucan (BG). Pharmacological inhibition or silencing of MGMT expression altered LPS stimulated pro-inflammatory cytokine productions in BG-trained bone marrow derived macrophages (BMMs). Targeted deletion of Mgmt in BMMs resulted in reduction of the trained responses both in vitro and in vivo models. The transcriptomic analysis revealed that the dampening trained immunity in MGMT KO BMMs is partially mediated by ATM/FXR/AMPK axis affecting the MAPK/mTOR/HIF1alpha pathways and the reduction in glycolysis function. Taken together, a failure to resolve a DNA damage may have consequences for innate immune memory. |
