| First Author | Lech M | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 8 | Pages | 1879-88 |
| PubMed ID | 18644972 | Mgi Jnum | J:138217 |
| Mgi Id | MGI:3804574 | Doi | 10.1084/jem.20072646 |
| Citation | Lech M, et al. (2008) Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens. J Exp Med 205(8):1879-88 |
| abstractText | The Sigirr gene (also known as Tir8) encodes for an orphan receptor of the Toll-like receptor (TLR)/interleukin 1 receptor family that inhibits TLR-mediated pathogen recognition in dendritic cells. Here, we show that Sigirr also inhibits the activation of dendritic cells and B cells upon exposure to RNA and DNA lupus autoantigens. To evaluate the functional role of Sigirr in the pathogenesis of systemic lupus erythematosus (SLE), we generated Sigirr-deficient C57BL/6-lpr/lpr mice. These mice developed a progressive lymphoproliferative syndrome followed by severe autoimmune lung disease and lupus nephritis within 6 mo of age as compared with the minor abnormalities observed in C57BL/6-lpr/lpr mice. Lack of Sigirr was associated with enhanced activation of dendritic cells and increased expression of multiple proinflammatory and antiapoptotic mediators. In the absence of Sigirr, CD4 T cell numbers were increased and CD4(+)CD25(+) T cell numbers were reduced. Furthermore, lack of Sigirr enhanced the activation and proliferation of B cells, including the production of autoantibodies against multiple nuclear lupus autoantigens. These data identify Sigirr as a novel SLE susceptibility gene in mice. |
