Abnormal T cell activation caused by the imbalance of the IL-1/IL-1R antagonist system is responsible for the development of experimental autoimmune encephalomyelitis.
IL-1 is a pro-inflammatory cytokine that plays an important role in inflammation and host responses to infection. We have previously shown that imbalances in the IL-1 and IL-1R antagonist (IL-1Ra) system cause the development of inflammatory diseases. To explore the role of the IL-1/IL-1Ra system in autoimmune disease, we analyzed myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in mice bearing targeted disruptions of the IL-1alpha, IL-1beta, IL-1alpha and IL-1beta (IL-1) or IL-1Ra genes. IL-1alpha/beta double-deficient (IL-1-/-) mice exhibited significant resistance to EAE induction with a significant reduction in disease severity, while IL-1alpha-/- or IL-1beta-/- mice developed EAE in a manner similar to wild-type mice. IL-1Ra-/- mice also developed MOG-induced EAE normally with pertussis toxin (PTx) administration. In contrast to wild-type mice, however, these mice were highly susceptible to EAE induction in the absence of PTx administration. We found that both IFN-gamma and IL-17 production and proliferation were reduced in IL-1-/- T cells upon stimulation with MOG, while IFN-gamma, IL-17 and tumor necrosis factor-alpha production and proliferation were enhanced in IL-1Ra-/- T cells. These observations suggest that the IL-1/IL-1Ra system is crucial for auto-antigen-specific T cell induction and contributes to the development of EAE.
Matsuki
Taizo
T
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Nakae
Susumu
S
Sudo
Katsuko
K
Horai
Reiko
R
Iwakura
Yoichiro
Y
D000595:Amino Acid Sequence; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D017472:Receptors, Interleukin-1 / Q000276:immunology; D012795:Sialoglycoproteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins