| First Author | Gelderman KA | Year | 2007 |
| Journal | J Clin Invest | Volume | 117 |
| Issue | 10 | Pages | 3020-8 |
| PubMed ID | 17909630 | Mgi Jnum | J:286664 |
| Mgi Id | MGI:6405997 | Doi | 10.1172/JCI31935 |
| Citation | Gelderman KA, et al. (2007) Macrophages suppress T cell responses and arthritis development in mice by producing reactive oxygen species. J Clin Invest 117(10):3020-8 |
| abstractText | Reduced capacity to produce ROS increases the severity of T cell-dependent arthritis in both mice and rats with polymorphisms in neutrophil cytosolic factor 1 (Ncf1) (p47phox). Since T cells cannot exert oxidative burst, we hypothesized that T cell responsiveness is downregulated by ROS produced by APCs. Macrophages have the highest burst capacity among APCs, so to study the effect of macrophage ROS on T cell activation, we developed transgenic mice expressing functional Ncf1 restricted to macrophages. Macrophage-restricted expression of functional Ncf1 restored arthritis resistance to the level of that of wild-type mice in a collagen-induced arthritis model but not in a T cell-independent anti-collagen antibody-induced arthritis model. T cell activation was downregulated and skewed toward Th2 in transgenic mice. In vitro, IL-2 production and T cell proliferation were suppressed by macrophage ROS, irrespective of T cell origin. IFN-gamma production, however, was independent of macrophage ROS but dependent on T cell origin. These effects were antigen dependent but not restricted to collagen type II. In conclusion, macrophage-derived ROS play a role in T cell selection, maturation, and differentiation, and also a suppressive role in T cell activation, and thereby mediate protection against autoimmune diseases like arthritis. |
