| First Author | Lee S | Year | 2022 |
| Journal | Biochem Biophys Res Commun | Volume | 629 |
| Pages | 171-175 | PubMed ID | 36122455 |
| Mgi Jnum | J:329992 | Mgi Id | MGI:7355784 |
| Doi | 10.1016/j.bbrc.2022.09.017 | Citation | Lee S, et al. (2022) Attenuation of regulatory T cell function by type I IFN signaling in an MDA5 gain-of-function mutant mouse model. Biochem Biophys Res Commun 629:171-175 |
| abstractText | Melanoma differentiation-associated gene 5 (MDA5) is an essential viral double-stranded RNA sensor to trigger antiviral immune responses, including type I interferon (IFN) induction. Aberrant activation of this viral sensor is known to cause autoimmune diseases designated as type I interferonopathies. However, the cell types responsible for these diseases and the molecular mechanisms behind their onset and development are still largely unknown. In this study, we revealed the attenuation of regulatory T cell (Treg) function by type I IFN signaling in a mouse model expressing a gain-of-function MDA5 G821S mutant. We found that experimental colitis induced by adoptive transfer of naive T cells in Rag2(-/-) mice was rescued by simultaneous transfer of Tregs from wild-type but not from the MDA5 mutant mice. Type I IFN receptor deficiency in the MDA5 mutant mice recovered the suppressive function of MDA5 mutant Tregs. These results suggest that constitutive MDA5 and type I IFN signaling in Tregs decreases the suppressive function of Tregs, potentially contributing to the onset and exacerbation of autoimmune disorders in interferonopathies. |
