| First Author | Webb LM | Year | 2019 |
| Journal | Front Immunol | Volume | 10 |
| Pages | 524 | PubMed ID | 30941147 |
| Mgi Jnum | J:294968 | Mgi Id | MGI:6458223 |
| Doi | 10.3389/fimmu.2019.00524 | Citation | Webb LM, et al. (2019) NF-kappaB/mTOR/MYC Axis Drives PRMT5 Protein Induction After T Cell Activation via Transcriptional and Non-transcriptional Mechanisms. Front Immunol 10:524 |
| abstractText | Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) mediated by CD4(+) T cells and modeled via experimental autoimmune encephalomyelitis (EAE). Inhibition of PRMT5, the major Type II arginine methyltransferase, suppresses pathogenic T cell responses and EAE. PRMT5 is transiently induced in proliferating memory inflammatory Th1 cells and during EAE. However, the mechanisms driving PRMT5 protein induction and repression as T cells expand and return to resting is currently unknown. Here, we used naive mouse and memory mouse and human Th1/Th2 cells as models to identify mechanisms controlling PRMT5 protein expression in initial and recall T cell activation. Initial activation of naive mouse T cells resulted in NF-kappaB-dependent transient Prmt5 transcription and NF-kappaB, mTOR and MYC-dependent PRMT5 protein induction. In murine memory Th cells, transcription and miRNA loss supported PRMT5 induction to a lesser extent than in naive T cells. In contrast, NF-kappaB/MYC/mTOR-dependent non-transcriptional PRMT5 induction played a major role. These results highlight the importance of the NF-kappaB/mTOR/MYC axis in PRMT5-driven pathogenic T cell expansion and may guide targeted therapeutic strategies for MS. |
