Differing outcome of experimental autoimmune encephalitis in macrophage/neutrophil- and T cell-specific gp130-deficient mice
Holz K, Prinz M, Brendecke SM, Hölscher A, Deng F, Mitrücker HW, Rose-John S, Hölscher C.
gp130 cytokines are differentially involved in regulating the T helper (H) 17- driven pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model of human multiple sclerosis. Interleukin (IL)-6 directly promotes the development of TH17 cells through the gp130/IL-6R complex. By contrast, IL-27 has been shown to suppress a TH17 immune response by gp130/IL-27R-alpha (α) receptor ligation. The IL-27-dependent regulation of a TH17 development could be mediated on the level of CD4 T cells. To further prove IL-6 to be responsible for the control of inflammation during EAE through gp130 on macrophages/neutrophils, we immunized LysMcreposIL- 6RloxP/loxP mice. In contrast to LysMcreposgp130loxP/loxP mice, neuropathology in MOG35-55-immunized macrophage/neutrophil-specific IL- 6R-deficient mice was not enhanced indicating that the alleviation of EAE through macrophage/neutrophil-gp130 is mediated independently of IL-6. Together, this different pathology in macrophage/neutrophil- and CD4 T cellspecific gp130-deficient mice suggests that gp130 cytokines modulate TH17 inflammation differentially by targeting distinct cell types.
