TY - JOUR
T1 - IL-6, IL-17 and Stat3 are required for auto-inflammatory syndrome development in mouse
AU - Oike, Takatsugu
AU - Kanagawa, Hiroya
AU - Sato, Yuiko
AU - Kobayashi, Tami
AU - Nakatsukasa, Hiroko
AU - Miyamoto, Kana
AU - Nakamura, Satoshi
AU - Kaneko, Yosuke
AU - Kobayashi, Shu
AU - Harato, Kengo
AU - Yoshimura, Akihiko
AU - Iwakura, Yoichiro
AU - Takeuchi, Tsutomu
AU - Matsumoto, Morio
AU - Nakamura, Masaya
AU - Niki, Yasuo
AU - Miyamoto, Takeshi
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Auto-inflammatory syndrome, a condition clinically distinct from rheumatoid arthritis, is characterized by systemic inflammation in tissues such as major joints, skin, and internal organs. Autonomous innate-immune activation is thought to promote this inflammation, but underlying pathological mechanisms have not been clarified nor are treatment strategies established. Here, we newly established a mouse model in which IL-1 signaling is conditionally activated in adult mice (hIL-1 cTg) and observed phenotypes similar to those seen in auto-inflammatory syndrome patients. In serum of hIL-1 cTg mice, IL-6 and IL-17 levels significantly increased, and signal transducer and activator of transcription 3 (Stat3) was activated in joints. When we crossed hIL-1 cTg with either IL-6- or IL-17-deficient mice or with Stat3 conditional knockout mice, phenotypes seen in hIL-1 cTg mice were significantly ameliorated. Thus, IL-6, IL-17 and Stat3 all represent potential therapeutic targets for this syndrome.
AB - Auto-inflammatory syndrome, a condition clinically distinct from rheumatoid arthritis, is characterized by systemic inflammation in tissues such as major joints, skin, and internal organs. Autonomous innate-immune activation is thought to promote this inflammation, but underlying pathological mechanisms have not been clarified nor are treatment strategies established. Here, we newly established a mouse model in which IL-1 signaling is conditionally activated in adult mice (hIL-1 cTg) and observed phenotypes similar to those seen in auto-inflammatory syndrome patients. In serum of hIL-1 cTg mice, IL-6 and IL-17 levels significantly increased, and signal transducer and activator of transcription 3 (Stat3) was activated in joints. When we crossed hIL-1 cTg with either IL-6- or IL-17-deficient mice or with Stat3 conditional knockout mice, phenotypes seen in hIL-1 cTg mice were significantly ameliorated. Thus, IL-6, IL-17 and Stat3 all represent potential therapeutic targets for this syndrome.
UR - https://www.scopus.com/pages/publications/85055454806
UR - https://www.scopus.com/pages/publications/85055454806#tab=citedBy
U2 - 10.1038/s41598-018-34173-5
DO - 10.1038/s41598-018-34173-5
M3 - Article
C2 - 30361689
AN - SCOPUS:85055454806
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 15783
ER -