The role of TNFalpha and IL-17 in the development of excess IL-1 signaling-induced inflammatory diseases in IL-1 receptor antagonist-deficient mice.
IL-1 receptor antagonist (IL-1Ra)-deficient mice spontaneously develop several inflammatory diseases, resembling rheumatoid arthritis, aortitis, and psoriasis in humans. As adoptive T cell transplantation could induce arthritis and aortitis in recipient mice, it was suggested that an autoimmune process is involved in the development of diseases. In contrast, as dermatitis developed in scid/scid-IL-IRa-deficient mice and could not be induced by T cell transfer, a T cell-independent mechanism was suggested. The expression of proinflammatory cytokines was augmented at the inflammatory sites. The development of arthritis and aortitis was significantly suppressed by the deficiency of TNFalpha or IL-17. The development of dermatitis was also inhibited by the deficiency of TNFalpha. These observations suggest that TNFalpha and IL-17 play a crucial role in the development of autoimmunity downstream of IL-1 signaling, and excess IL-1 signaling-induced TNFalpha also induces skin inflammation in a T cell-independent manner.
Ishigame
H
H
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Japan.
Nakajima
A
A
Saijo
S
S
Komiyama
Y
Y
Nambu
A
A
Matsuki
T
T
Nakae
S
S
Horai
R
R
Kakuta
S
S
Iwakura
Y
Y
D000818:Animals; D001025:Aortitis / Q000276:immunology / Q000473:pathology; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology; D001327:Autoimmune Diseases / Q000276:immunology*; D003872:Dermatitis / Q000276:immunology / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D007375:Interleukin-1; D020381:Interleukin-17; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha