Figure 1: The inflammation amplifier
A, A combination of IL-17 and IL-6 in causes a synergistic effect on the induction of inflammation-amplifier target chemokines such as Ccl20 in nonimmune cells including fibroblasts, endothelial cells and certain synovial cells. B, The synergistic effect seen in A requires the concomitant activation of two transcription factors, NFkappa-B and STAT3. In the case of autoimmune diseases, Th17-derived IL-17 induces an initial, low amount of IL-6 from nonimmune cells via NFkappa-B activation. Secreted IL-6 together with IL-17 form an amplification loop, producing an excessive amount of target genes including many inflammatory chemokines such as Ccl20 and CCL2 etc. Consequently, various immune cells are recruited at the region around the target cells via chemokine expression and inflammation takes place. Persistent activation of the inflammation amplifier, as is the case in F759 mice, drives a chronic inflammation. IL-7, a target of the amplifier, derived from non-immune cells aids in the proliferation and survival of Th17 cells.