| First Author | Fueyo-González F | Year | 2022 |
| Journal | Immunity | Volume | 55 |
| Issue | 3 | Pages | 459-474.e7 |
| PubMed ID | 35148827 | Mgi Jnum | J:324835 |
| Mgi Id | MGI:7281904 | Doi | 10.1016/j.immuni.2022.01.011 |
| Citation | Fueyo-Gonzalez F, et al. (2022) Interferon-beta acts directly on T cells to prolong allograft survival by enhancing regulatory T cell induction through Foxp3 acetylation. Immunity 55(3):459-474.e7 |
| abstractText | Type I interferons (IFNs) are pleiotropic cytokines with potent antiviral properties that also promote protective T cell and humoral immunity. Paradoxically, type I IFNs, including the widely expressed IFNbeta, also have immunosuppressive properties, including promoting persistent viral infections and treating T-cell-driven, remitting-relapsing multiple sclerosis. Although associative evidence suggests that IFNbeta mediates these immunosuppressive effects by impacting regulatory T (Treg) cells, mechanistic links remain elusive. Here, we found that IFNbeta enhanced graft survival in a Treg-cell-dependent murine transplant model. Genetic conditional deletion models revealed that the extended allograft survival was Treg cell-mediated and required IFNbeta signaling on T cells. Using an in silico computational model and analysis of human immune cells, we found that IFNbeta directly promoted Treg cell induction via STAT1- and P300-dependent Foxp3 acetylation. These findings identify a mechanistic connection between the immunosuppressive effects of IFNbeta and Treg cells, with therapeutic implications for transplantation, autoimmunity, and malignancy. |
