| First Author | Nakahama T | Year | 2018 |
| Journal | EMBO Rep | Volume | 19 |
| Issue | 12 | PubMed ID | 30361393 |
| Mgi Jnum | J:269483 | Mgi Id | MGI:6259981 |
| Doi | 10.15252/embr.201846303 | Citation | Nakahama T, et al. (2018) ADAR1-mediated RNA editing is required for thymic self-tolerance and inhibition of autoimmunity. EMBO Rep 19(12) |
| abstractText | T cells play a crucial role in the adaptive immune system, and their maturation process is tightly regulated. Adenosine deaminase acting on RNA 1 (ADAR1) is the enzyme responsible for adenosine-to-inosine RNA editing in dsRNAs, and loss of ADAR1 activates the innate immune sensing response via melanoma differentiation-associated protein 5 (MDA5), which interprets unedited dsRNA as non-self. Although ADAR1 is highly expressed in the thymus, its role in the adaptive immune system, especially in T cells, remains elusive. Here, we demonstrate that T cell-specific deletion of Adar1 in mice causes abnormal thymic T cell maturation including impaired negative selection and autoimmunity such as spontaneous colitis. This is caused by excessive expression of interferon-stimulated genes, which reduces T cell receptor (TCR) signal transduction, due to a failure of RNA editing in ADAR1-deficient thymocytes. Intriguingly, concurrent deletion of MDA5 restores thymocyte maturation and prevents colitis. These findings suggest that prevention of MDA5 sensing of endogenous dsRNA by ADAR1-mediated RNA editing is required for preventing both innate immune responses and T cell-mediated autoimmunity. |
