STAT1-mediated induction of Ly6c-expressing macrophages are involved in the pathogenesis of an acute colitis model

Kii, Shuhei; Kitamura, Hidemitsu; Hashimoto, Shinichi; Ikeo, Kazuho; Ichikawa, Nobuki; Yoshida, Tadashi; Homma, Shigenori; Tanino, Mishie; Taketomi, Akinobu

STAT1-mediated induction of Ly6c-expressing macrophages are involved in the pathogenesis of an acute colitis model

Kii, Shuhei; Kitamura, Hidemitsu; Hashimoto, Shinichi et al.

Inflammation Research, 2022, 71(9), 1079-1094

Permalink : https://hdl.handle.net/2115/90332

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アクセス権	open access
URI	https://hdl.handle.net/2115/90332
タイトル	STAT1-mediated induction of Ly6c-expressing macrophages are involved in the pathogenesis of an acute colitis model
著者	Kii, Shuhei ; Kitamura, Hidemitsu ; Hashimoto, Shinichi ; Ikeo, Kazuho ; Ichikawa, Nobuki ; Yoshida, Tadashi ; Homma, Shigenori ; Tanino, Mishie ; Taketomi, Akinobu
著者名 Kii, Shuhei
e-Rad_Researcher 40360531 著者名 Kitamura, Hidemitsu
著者名 Hashimoto, Shinichi
著者名 Ikeo, Kazuho
著者名 Ichikawa, Nobuki
著者名 Yoshida, Tadashi
e-Rad_Researcher 30533674 著者名 Homma, Shigenori
著者名 Tanino, Mishie
e-Rad_Researcher 70363364 著者名 Taketomi, Akinobu
言語	英語
キーワード	Signal transducer and activator of transcription 1
	CCR2
	Ly6c
	Macrophages
	Inflammatory bowel disease
発行日	2022-09-01
収録物名	Inflammation Research
巻(号)	71(9)
ページ	1079-1094
抄録	Background The development of inflammatory bowel diseases is thought to be multifactorial, but the exact steps in pathogenesis are poorly understood. In this study, we investigated involvement of the activation of STAT1 signal pathway in the pathogenesis of an acute colitis model. Methods A dextran sulfate sodium-induced acute colitis model was established by using wild-type C57BL/6 mice and STAT1-deficient mice. Disease indicators such as body weight loss and clinical score, induction of cytokines, chemokines, and inflammatory cells were evaluated in the acute colitis model. Results Disease state was significantly improved in the acute colitis model using STAT1-deficient mice compared with wild-type mice. The induction of Ly6c-highly expressing cells in colorectal tissues was attenuated in STAT1-deficient mice. IL-6, CCL2, and CCR2 gene expressions in Ly6c-highly expressing cells accumulated in the inflamed colon tissues and were significantly higher than in Ly6c-intermediate-expressing cells, whereas TNF-α and IFN-α/β gene expression was higher in Ly6c-intermediate-expressing cells. Blockade of CCR2-mediated signaling significantly reduced the disease state in the acute colitis model. Conclusions Two different types of Ly6c-expressing macrophages are induced in the inflamed tissues through the IFN-α/β-STAT1-mediated CCL2/CCR2 cascade and this is associated with the pathogenesis such as onset, exacerbation, and subsequent chronicity of acute colitis.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s00011-022-01620-z
PISSN	1023-3830
EISSN	1420-908X
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1007/s00011-022-01620-z