| First Author | Miyagawa F | Year | 2020 |
| Journal | J Transl Autoimmun | Volume | 3 |
| Pages | 100060 | PubMed ID | 32743540 |
| Mgi Jnum | J:303382 | Mgi Id | MGI:6512133 |
| Doi | 10.1016/j.jtauto.2020.100060 | Citation | Miyagawa F, et al. (2020) Inflammatory monocyte-derived dendritic cells mediate autoimmunity in murine model of systemic lupus erythematosus. J Transl Autoimmun 3:100060 |
| abstractText | Using a mouse model of systemic lupus erythematosus (SLE), we recently demonstrated that the two major manifestations of SLE are mechanistically independent because the type I IFN pathway leads to the autoantibody production whereas the NF-kappaB activation is sufficient for the development of glomerulonephritis. To further advance our understandings on the molecular pathways regulating the development of SLE, we studied the role of IRF8 because it controls both type I IFN and NF-kappaB pathways and saw that IRF8-deficient mice failed to develop either glomerulonephritis or the autoantibody production. Furthermore, these genetically engineered mice prompted us to realize the important role of Ly6C(high) inflammatory monocytes in the development of SLE. These monocytes migrate to the peritoneal cavity in WT and IRF7-deficient mice but not in IRF8-deficient mice, and there they produce both type I IFN and proinflammatory cytokines in WT mice, while in IRF7-deficient mice they only produce proinflammatory cytokines. Upon migration to the spleen, Ly6C(high) inflammatory monocytes differentiate into dendritic cells (DCs) which are capable of producing proinflammatory cytokines in response to dsDNA autoantigen. Collectively, type I IFN produced from inflammatory monocytes/monocyte-derived DCs might be essential for autoantibody production whereas proinflammatory cytokines produced from them might mediate tissue damages in this model. Our study reveals a specialized role for monocyte-derived antigen presenting cells in autoimmunity. Plasticity of monocyte might play an important role not only in the pathogenesis of the disease but also in flare-ups of the disease. |
