IL-6, IL-17 and Stat3 are required for auto-inflammatory syndrome development in mouse

Takatsugu Oike, Hiroya Kanagawa, Yuiko Sato, Tami Kobayashi, Hiroko Nakatsukasa, Kana Miyamoto, Satoshi Nakamura, Yosuke Kaneko, Shu Kobayashi, Kengo Harato, Akihiko Yoshimura, Yoichiro Iwakura, Tsutomu Takeuchi, Morio Matsumoto, Masaya Nakamura, Yasuo Niki, Takeshi Miyamoto

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Abstract

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.

Original languageEnglish
Article number15783
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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STAT3 Transcription Factor
Interleukin-17
Interleukin-6
Joints
Inflammation
Phenotype
Interleukin-1
Knockout Mice
Rheumatoid Arthritis
Skin
Therapeutics
Serum

ASJC Scopus subject areas

  • General

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IL-6, IL-17 and Stat3 are required for auto-inflammatory syndrome development in mouse. / Oike, Takatsugu; Kanagawa, Hiroya; Sato, Yuiko; Kobayashi, Tami; Nakatsukasa, Hiroko; Miyamoto, Kana; Nakamura, Satoshi; Kaneko, Yosuke; Kobayashi, Shu; Harato, Kengo; Yoshimura, Akihiko; Iwakura, Yoichiro; Takeuchi, Tsutomu; Matsumoto, Morio; Nakamura, Masaya; Niki, Yasuo; Miyamoto, Takeshi.

In: Scientific Reports, Vol. 8, No. 1, 15783, 01.12.2018.

Research output: Contribution to journalArticle

Oike, Takatsugu ; Kanagawa, Hiroya ; Sato, Yuiko ; Kobayashi, Tami ; Nakatsukasa, Hiroko ; Miyamoto, Kana ; Nakamura, Satoshi ; Kaneko, Yosuke ; Kobayashi, Shu ; Harato, Kengo ; Yoshimura, Akihiko ; Iwakura, Yoichiro ; Takeuchi, Tsutomu ; Matsumoto, Morio ; Nakamura, Masaya ; Niki, Yasuo ; Miyamoto, Takeshi. / IL-6, IL-17 and Stat3 are required for auto-inflammatory syndrome development in mouse. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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AU - Miyamoto, Kana

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