| First Author | Akiyama C | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 4 | Pages | 835-843 |
| PubMed ID | 31324723 | Mgi Jnum | J:279671 |
| Mgi Id | MGI:6343154 | Doi | 10.4049/jimmunol.1801617 |
| Citation | Akiyama C, et al. (2019) Conditional Upregulation of IFN-alpha Alone Is Sufficient to Induce Systemic Lupus Erythematosus. J Immunol 203(4):835-843 |
| abstractText | The cause of systemic lupus erythematosus (SLE) is unknown. IFN-alpha has been suggested as a causative agent of SLE; however, it was not proven, and to what extent and how IFN-alpha contributes to the disease is unknown. We studied the contribution of IFN-alpha to SLE by generating inducible IFN-alpha transgenic mice and directly show that conditional upregulation of IFN-alpha alone induces a typical manifestation of SLE in the mice not prone to autoimmunity, such as serum immune complex, autoantibody against dsDNA (anti-dsDNA Ab), and the organ manifestations classical to SLE, such as immune complex-deposited glomerulonephritis, classical splenic onion-skin lesion, alopecia, epidermal liquefaction, and positive lupus band test of the skin. In the spleen of mice, activated effector CD4 T cells, IFN-gamma-producing CD8 T cells, B220(+)CD86(+) cells, and CD11c(+)CD86(+) cells were increased, and the T cells produced increased amounts of IL-4, IL-6, IL-17, and IFN-gamma and decreased IL-2. In particular, activated CD3(+)CD4(-)CD8(-) double-negative T cells positive for TCRalphabeta, B220, CD1d-teteramer, PD-1, and Helios (that produced increased amounts of IFN-gamma, IL-4, IL-17, and TNF-alpha) were significantly expanded. They infiltrated into kidney and induced de novo glomerulonephritis and alopecia when transferred into naive recipients. Thus, sole upregulation of IFN-alpha is sufficient to induce SLE, and the double-negative T cells expanded by IFN-alpha are directly responsible for the organ manifestations, such as lupus skin disease or nephritis. |
