| First Author | George-Chandy A | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 4 | Pages | 1118-26 |
| PubMed ID | 18383034 | Mgi Jnum | J:133769 |
| Mgi Id | MGI:3784124 | Doi | 10.1002/eji.200737348 |
| Citation | George-Chandy A, et al. (2008) Th17 development and autoimmune arthritis in the absence of reactive oxygen species. Eur J Immunol 38(4):1118-26 |
| abstractText | Dendritic cells (DC) express a functional NADPH oxidase and produce reactive oxygen species (ROS) upon interaction with microbes and T cells. Exposure to ROS leads to DC activation and maturation, as evidenced by phenotypic and functional changes. We have evaluated how endogenous ROS production affects the cytokine secretion pattern and T cell-activating capacity of bone marrow-derived murine DC. DC treated with ROS scavengers, as well as DC from mice that lack a functional NADPH oxidase (and thereby inherently deficient in ROS production) produced significantly increased levels of IL-1beta, IL-6, TNF-alpha and TGF-beta in response to microbial activation. DC deficient in ROS production induced high levels of IFN-gamma and IL-17 in responding T cells after Ag-specific or superantigen-induced activation. Finally, we show that ROS deficiency affected the induction of a T cell-dependent inflammatory condition, collagen-induced arthritis (CIA). C57BL/6 mice that lack a functional NADPH oxidase developed a severe and erosive CD4-dependent CIA, whereas the majority of the congenic wild-type animals remained healthy. These data suggest that ROS act as immunomodulators in DC-driven T cell activation and perhaps also in T cell-dependent immunopathology. |
