Autophagy promotes citrullination of VIM (vimentin) and its interaction with major histocompatibility complex class II in synovial fibroblasts

Sugawara, Eri; Kato, Masaru; Kudo, Yuki; Lee, Wenshi; Hisada, Ryo; Fujieda, Yuichiro; Oku, Kenji; Bohgaki, Toshiyuki; Amengual, Olga; Yasuda, Shinsuke; Onodera, Tomohiro; Hatakeyama, Shigetsugu; Atsumi, Tatsuya

Autophagy promotes citrullination of VIM (vimentin) and its interaction with major histocompatibility complex class II in synovial fibroblasts

Sugawara, Eri; Kato, Masaru; Kudo, Yuki et al.

Autophagy, 2020, 16(5), 946-955

Permalink : https://hdl.handle.net/2115/81113

このアイテムのアクセス数:528件（2026-08-12 05:16 集計）

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Autophagy_Manuscript Sugawara ver 3.8	pdf	12.2 MB	536
Supplementary figure 1.8	docx	17.7 MB	209

論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/81113
タイトル	Autophagy promotes citrullination of VIM (vimentin) and its interaction with major histocompatibility complex class II in synovial fibroblasts
著者	Sugawara, Eri ; Kato, Masaru ; Kudo, Yuki ; Lee, Wenshi ; Hisada, Ryo ; Fujieda, Yuichiro ; Oku, Kenji ; Bohgaki, Toshiyuki ; Amengual, Olga ; Yasuda, Shinsuke ; Onodera, Tomohiro ; Hatakeyama, Shigetsugu ; Atsumi, Tatsuya
著者名 Sugawara, Eri
e-Rad_Researcher 10755896 著者名 Kato, Masaru
著者名 Kudo, Yuki
著者名 Lee, Wenshi
著者名 Hisada, Ryo
e-Rad_Researcher 70790872 著者名 Fujieda, Yuichiro
e-Rad_Researcher 70544295 著者名 Oku, Kenji
e-Rad_Researcher 50431367 著者名 Bohgaki, Toshiyuki
e-Rad_Researcher 10636939 著者名 Amengual, Olga
e-Rad_Researcher 00374231 著者名 Yasuda, Shinsuke
e-Rad_Researcher 70547174 著者名 Onodera, Tomohiro
e-Rad_Researcher 70294973 著者名 Hatakeyama, Shigetsugu
e-Rad_Researcher 20301905 著者名 Atsumi, Tatsuya
言語	英語
キーワード	Autophagy
	citrullination
	MHC class II
	rheumatoid arthritis
	vimentin
発行日	2020-05-03
出版者	Taylor & Francis
収録物名	Autophagy
巻(号)	16(5)
ページ	946-955
抄録	We aimed to investigate the involvement of macroautophagy/autophagy in autoimmunity in rheumatoid arthritis (RA) through citrullination of VIM (vimentin) and its interaction with MHC class II in synovial fibroblasts (SFs). The cell surface expression of MHC class II and B7 costimulatory molecules on SFs was analyzed by flow cytometry after treatment with IFNG/IFN-gamma (interferon gamma). Intracellular citrullinated autoantigens in SFs were analyzed by immunoblotting using serum from anti-citrullinated peptide antibodies (ACPA)-positive patient as a primary antibody. SFs were incubated in serum-free medium or treated with proteasome inhibitor MG132 to induce autophagy. An autophagy inhibitor 3-methyladenin (3-MA) was used. Intracellular citrullinated VIM (cVIM) was evaluated by immunoblotting and immunocytochemistry. The interaction between MHC class II and cVIM was evaluated with co-immunoprecipitation and proximity ligation assay (PLA). We demonstrated that MHC class II, CD274/B7-H1 and PDCD1LG2/B7-DC were expressed on SFs following treatment with IFNG whereas CD276/B7-H3 was detected on SFs regardless of the presence of IFNG. ACPA-positive sera recognized a 54 kDa protein in SFs. By immunoprecipitation, the 54 kDa protein recognized by RA sera was revealed to be cVIM. Following induction of autophagy, intracellular cVIM was increased in SFs but the effect was canceled by 3-MA. The interaction between MHC class II and cVIM was demonstrated by co-immunoprecipitation. Furthermore, PLA revealed the significant increase of MHC class II-cVIM interaction following induction of autophagy. Our findings suggest that SFs may contribute to the autoimmunity in RA through citrullination of VIM and its interaction with MHC class II promoted by autophagy.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This is an Accepted Manuscript of an article published by Taylor & Francis in Autophagy on 03 May 2020, available online: http://www.tandfonline.com/10.1080/15548627.2019.1664144.
PISSN	1554-8627
EISSN	1554-8635
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1080/15548627.2019.1664144