| First Author | Gall A | Year | 2012 |
| Journal | Immunity | Volume | 36 |
| Issue | 1 | Pages | 120-31 |
| PubMed ID | 22284419 | Mgi Jnum | J:181257 |
| Mgi Id | MGI:5310667 | Doi | 10.1016/j.immuni.2011.11.018 |
| Citation | Gall A, et al. (2012) Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. Immunity 36(1):120-31 |
| abstractText | The type I interferon (IFN) response initiated by detection of nucleic acids is important for antiviral defense but is also associated with specific autoimmune diseases. Mutations in the human 3' repair exonuclease 1 (Trex1) gene cause Aicardi-Goutieres syndrome (AGS), an IFN-associated autoimmune disease. However, the source of the type I IFN response and the precise mechanisms of disease in AGS remain unknown. Here, we demonstrate that Trex1 is an essential negative regulator of the STING-dependent antiviral response. We used an in vivo reporter of IFN activity in Trex1-deficient mice to localize the initiation of disease to nonhematopoietic cells. These IFNs drove T cell-mediated inflammation and an autoantibody response that targeted abundant, tissue-restricted autoantigens. However, B cells contributed to mortality independently of T cell-mediated tissue damage. These findings reveal a stepwise progression of autoimmune disease in Trex1-deficient mice, with implications for the treatment of AGS and related disorders. |
