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

• Published in: Scientific reports Vol. 7; no. 1; pp. 5506 - 13
• Main Authors: Lee, Seung Hoon, Kim, Eun-Kyung, Kwon, Jeong-Eun, Lee, Jin-Kwan, Lee, DoHyeong, Kim, Se-Young, Seo, Hyeon-Beom, Na, Hyun Sik, Jung, KyoungAh, Kwok, Seung-Ki, Lee, Chang-Woo, Park, Sung-Hwan, Cho, Mi-La
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14-07-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 13/31; 13/44; 13/51; 42/109; 42/44; 631/250/256; 631/250/38; Animals; Arthritis; Arthritis, Rheumatoid - chemically induced; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - therapy; Cell activation; Cell differentiation; Cell Differentiation - drug effects; Cell-mediated immunity; Collagen - adverse effects; Disease Models, Animal; Gene regulation; Genetic Vectors - administration & dosage; Genetic Vectors - pharmacology; Helper cells; Humanities and Social Sciences; Inflammation; Interleukin 17; Lymphocyte Activation; Lymphocytes B; Lymphocytes T; Male; Mice; multidisciplinary; NIH 3T3 Cells; Osteoclastogenesis; Phosphoprotein Phosphatases - genetics; Phosphoprotein Phosphatases - metabolism; Science; Science (multidisciplinary); Signal Transduction - drug effects; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Th17 Cells - immunology; Transcription
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-05421-x

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.