IL-23 is critical in the induction but not in the effector phase of experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE), a T cell-mediated inflammatory disease of the CNS, is a rodent model of human multiple sclerosis. IL-23 is one of the critical cytokines in EAE development and is currently believed to be involved in the maintenance of encephalitogenic responses during the tissue damage effector phase of the disease. In this study, we show that encephalitogenic T cells from myelin oligodendrocyte glycopeptide (MOG)-immunized wild-type (WT) mice caused indistinguishable disease when adoptively transferred to WT or IL-23-deficient (p19 knockout (KO)) recipient mice, demonstrating that once encephalitogenic cells have been generated, EAE can develop in the complete absence of IL-23. Furthermore, IL-12/23 double-deficient (p35/p19 double KO) recipient mice developed EAE that was indistinguishable from WT recipients, indicating that IL-12 did not compensate for IL-23 deficiency during the effector phase of EAE. In contrast, MOG-specific T cells from p19KO mice induced EAE with delayed onset and much lower severity when transferred to WT recipient mice as compared with the EAE that was induced by cells from WT controls. MOG-specific T cells from p19KO mice were highly deficient in the production of IFN-gamma, IL-17A, and TNF, indicating that IL-23 plays a critical role in development of encephalitogenic T cells and facilitates the development of T cells toward both Th1 and Th17 pathways.
Thakker
Paresh
P
Department of Inflammation, Wyeth Research, Cambridge, MA 02140, USA. pthakker@wyeth.com
Leach
Michael W
MW
Kuang
Wen
W
Benoit
Stephen E
SE
Leonard
John P
JP
Marusic
Suzana
S
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000172:deficiency / Q000276:immunology*; D053760:Interleukin-23 Subunit p19 / Q000172:deficiency / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation
C508859:Il12a protein, mouse; C508841:Il23a protein, mouse; D053765:Interleukin-12 Subunit p35; D053760:Interleukin-23 Subunit p19; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein