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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Main Authors: 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
Format: Article
Language:English
Published: Nature Publishing Group 2017-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-05421-x
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spelling doaj-1c1c977a45ce4269ab9119dafc2fbdfa2020-12-08T02:12:26ZengNature Publishing GroupScientific Reports2045-23222017-07-017111310.1038/s41598-017-05421-xSsu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activationSeung Hoon Lee0Eun-Kyung Kim1Jeong-Eun Kwon2Jin-Kwan Lee3DoHyeong Lee4Se-Young Kim5Hyeon-Beom Seo6Hyun Sik Na7KyoungAh Jung8Seung-Ki Kwok9Chang-Woo Lee10Sung-Hwan Park11Mi-La Cho12The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan UniversityDepartment of Molecular Cell Biology, Sungkyunkwan University School of MedicineThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaImpact BiotechDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan UniversityThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaAbstract 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.https://doi.org/10.1038/s41598-017-05421-x
collection DOAJ
language English
format Article
sources DOAJ
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
spellingShingle 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
Scientific Reports
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 Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2017-07-01
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.
url https://doi.org/10.1038/s41598-017-05421-x
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