Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation

Abstract Signal transducer and activator of transcription 3 (STAT3) orchestrates the differentiation of several cell types, including interleukin-17 (IL-17)-releasing Th17 cells. Dysregulation of Th17 cells results in chronic inflammatory responses. Ssu72 is a C-terminal domain phosphatase required...

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Autores principales:	Seung Hoon Lee, Eun-Kyung Kim, Jeong-Eun Kwon, Jin-Kwan Lee, DoHyeong Lee, Se-Young Kim, Hyeon-Beom Seo, Hyun Sik Na, KyoungAh Jung, Seung-Ki Kwok, Chang-Woo Lee, Sung-Hwan Park, Mi-La Cho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1c1c977a45ce4269ab9119dafc2fbdfa
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spelling	oai:doaj.org-article:1c1c977a45ce4269ab9119dafc2fbdfa2021-12-02T16:07:06ZSsu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation10.1038/s41598-017-05421-x2045-2322https://doaj.org/article/1c1c977a45ce4269ab9119dafc2fbdfa2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05421-xhttps://doaj.org/toc/2045-2322Abstract Signal transducer and activator of transcription 3 (STAT3) orchestrates the differentiation of several cell types, including interleukin-17 (IL-17)-releasing Th17 cells. Dysregulation of Th17 cells results in chronic inflammatory responses. Ssu72 is a C-terminal domain phosphatase required for transcriptional regulation. However, the mechanism by which Ssu72 affects STAT3 activation and Th17 cell differentiation is unclear. Here, we found that Ssu72 overexpression suppresses STAT3 activation and Th17 cell responses in vitro. A systemic infusion of Ssu72 attenuates experimental autoimmune arthritis by reducing STAT3 activity and the differentiation of Th17 cells. It also reduces joint destruction, serum immunoglobulin concentrations and osteoclastogenesis but increases the number of marginal zone B cells and B10 cells. These effects are associated with reduced p-STAT3 levels and the suppression of Th17 cell formation in vivo. Based on these data, Ssu72 is related to STAT3 activation and the inflammatory response; and Ssu72 overexpression in T-cell-mediated immunity has potential utility for the treatment of autoimmune arthritis.Seung Hoon LeeEun-Kyung KimJeong-Eun KwonJin-Kwan LeeDoHyeong LeeSe-Young KimHyeon-Beom SeoHyun Sik NaKyoungAh JungSeung-Ki KwokChang-Woo LeeSung-Hwan ParkMi-La ChoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seung Hoon Lee Eun-Kyung Kim Jeong-Eun Kwon Jin-Kwan Lee DoHyeong Lee Se-Young Kim Hyeon-Beom Seo Hyun Sik Na KyoungAh Jung Seung-Ki Kwok Chang-Woo Lee Sung-Hwan Park Mi-La Cho Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation
description	Abstract Signal transducer and activator of transcription 3 (STAT3) orchestrates the differentiation of several cell types, including interleukin-17 (IL-17)-releasing Th17 cells. Dysregulation of Th17 cells results in chronic inflammatory responses. Ssu72 is a C-terminal domain phosphatase required for transcriptional regulation. However, the mechanism by which Ssu72 affects STAT3 activation and Th17 cell differentiation is unclear. Here, we found that Ssu72 overexpression suppresses STAT3 activation and Th17 cell responses in vitro. A systemic infusion of Ssu72 attenuates experimental autoimmune arthritis by reducing STAT3 activity and the differentiation of Th17 cells. It also reduces joint destruction, serum immunoglobulin concentrations and osteoclastogenesis but increases the number of marginal zone B cells and B10 cells. These effects are associated with reduced p-STAT3 levels and the suppression of Th17 cell formation in vivo. Based on these data, Ssu72 is related to STAT3 activation and the inflammatory response; and Ssu72 overexpression in T-cell-mediated immunity has potential utility for the treatment of autoimmune arthritis.
format	article
author	Seung Hoon Lee Eun-Kyung Kim Jeong-Eun Kwon Jin-Kwan Lee DoHyeong Lee Se-Young Kim Hyeon-Beom Seo Hyun Sik Na KyoungAh Jung Seung-Ki Kwok Chang-Woo Lee Sung-Hwan Park Mi-La Cho
author_facet	Seung Hoon Lee Eun-Kyung Kim Jeong-Eun Kwon Jin-Kwan Lee DoHyeong Lee Se-Young Kim Hyeon-Beom Seo Hyun Sik Na KyoungAh Jung Seung-Ki Kwok Chang-Woo Lee Sung-Hwan Park Mi-La Cho
author_sort	Seung Hoon Lee
title	Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation
title_short	Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation
title_full	Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation
title_fullStr	Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation
title_full_unstemmed	Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation
title_sort	ssu72 attenuates autoimmune arthritis via targeting of stat3 signaling and th17 activation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1c1c977a45ce4269ab9119dafc2fbdfa
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Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation

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