| First Author | Huang X | Year | 2015 |
| Journal | Cell Rep | Volume | 12 |
| Issue | 7 | Pages | 1120-32 |
| PubMed ID | 26257170 | Mgi Jnum | J:277593 |
| Mgi Id | MGI:6274104 | Doi | 10.1016/j.celrep.2015.07.021 |
| Citation | Huang X, et al. (2015) Neutrophils Regulate Humoral Autoimmunity by Restricting Interferon-gamma Production via the Generation of Reactive Oxygen Species. Cell Rep 12(7):1120-32 |
| abstractText | Here, we examine the mechanism by which plasmacytoid dendritic cells (pDCs) and type I interferons promote humoral autoimmunity. In an amyloid-induced experimental autoimmune model, neutrophil depletion enhanced anti-nuclear antibody development, which correlated with heightened IFN-gamma production by natural killer (NK) cells. IFN-alpha/beta produced by pDCs activated NK cells via IL-15 induction. Neutrophils released reactive oxygen species (ROS), which negatively modulated the levels of IL-15, thereby inhibiting IFN-gamma production. Mice deficient in NADPH oxidase 2 produced increased amounts of IFN-gamma and developed augmented titers of autoantibodies. Both the pDC-IFN-alpha/beta pathway and IFN-gamma were indispensable in stimulating humoral autoimmunity. Male NZB/W F1 mice expressed higher levels of superoxide than their female lupus-prone siblings, and depletion of neutrophils resulted in spontaneous NK cell and autoimmune B cell activation. Our findings suggest a regulatory role for neutrophils in vivo and highlight the importance of an NK-IFN-gamma axis downstream of the pDC-IFN-alpha/beta pathway in systemic autoimmunity. |
