Interleukin 18–independent engagement of interleukin 18 receptor-α is required for autoimmune inflammation

I Gutcher, E Urich, K Wolter, M Prinz, B Becher - Nature immunology, 2006 - nature.com
I Gutcher, E Urich, K Wolter, M Prinz, B Becher
Nature immunology, 2006nature.com
Abstract T helper type 1 (TH1) lymphocytes are considered to be the main pathogenic cell
type responsible for organ-specific autoimmune inflammation. As interleukin 18 (IL-18) is a
cofactor with IL-12 in promoting TH1 cell development, we examined the function of IL-18
and its receptor, IL-18R, in autoimmune central nervous system inflammation. Similar to IL-
12-deficient mice, IL-18-deficient mice were susceptible to experimental autoimmune
encephalomyelitis. In contrast, IL-18Rα-deficient mice were resistant to experimental …
Abstract
T helper type 1 (TH1) lymphocytes are considered to be the main pathogenic cell type responsible for organ-specific autoimmune inflammation. As interleukin 18 (IL-18) is a cofactor with IL-12 in promoting TH1 cell development, we examined the function of IL-18 and its receptor, IL-18R, in autoimmune central nervous system inflammation. Similar to IL-12-deficient mice, IL-18-deficient mice were susceptible to experimental autoimmune encephalomyelitis. In contrast, IL-18Rα-deficient mice were resistant to experimental autoimmune encephalomyelitis, indicating involvement of an IL-18Rα ligand other than IL-18 with encephalitogenic properties. Moreover, engagement of IL-18Rα on antigen-presenting cells was required for the generation of pathogenic IL-17-producing T helper cells. Thus, IL-18 and TH1 cells are dispensable, whereas IL-18Rα and IL-17-producing T helper cells are required, for autoimmune central nervous system inflammation.
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