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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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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