Interleukin 18-independent engagement of interleukin 18 receptor-alpha is required for autoimmune inflammation.
T helper type 1 (T(H)1) 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 T(H)1 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-18R alpha-deficient mice were resistant to experimental autoimmune encephalomyelitis, indicating involvement of an IL-18R alpha ligand other than IL-18 with encephalitogenic properties. Moreover, engagement of IL-18R alpha on antigen-presenting cells was required for the generation of pathogenic IL-17-producing T helper cells. Thus, IL-18 and T(H)1 cells are dispensable, whereas IL-18R alpha and IL-17-producing T helper cells are required, for autoimmune central nervous system inflammation.
Gutcher
Ilona
I
Neuroimmunology Unit, Neurology Clinic, University of Zurich, 8057 Zurich, Switzerland.
Urich
Eduard
E
Wolter
Karina
K
Prinz
Marco
M
Becher
Burkhard
B
D000818:Animals; D000938:Antigen-Presenting Cells / Q000737:chemistry / Q000276:immunology; D000941:Antigens / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018664:Interleukin-12 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D020382:Interleukin-18 / Q000235:genetics / Q000502:physiology; D053759:Interleukin-23 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008934:Mitogens / Q000276:immunology; D053724:Receptors, Interleukin-18 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology*
D000941:Antigens; D020381:Interleukin-17; D020382:Interleukin-18; D053759:Interleukin-23; D008934:Mitogens; D053724:Receptors, Interleukin-18; D018664:Interleukin-12