Protein inhibitor of activated STAT3 reduces peripheral arthritis and gut inflammation and regulates the Th17/Treg cell imbalance via STAT3 signaling in a mouse model of spondyloarthritis

• Published in: Journal of translational medicine 2019-01, Vol.17 (1), p.18-18, Article 18
• Main Authors: Min, Hong-Ki, Choi, JeongWon, Lee, Seon-Yeong, Seo, Hyeon-Beom, Jung, KyungAh, Na, Hyun Sik, Ryu, Jun-Geol, Kwok, Seung-Ki, Cho, Mi-La, Park, Sung-Hwan
• Format: Article
• Language: English
• Subjects: Animals; Ankylosing spondylitis; Arthritis; Bone morphogenetic protein 2; Bone Morphogenetic Proteins - metabolism; Cell Differentiation; Confocal microscopy; Cytokines; Cytokines - metabolism; Development and progression; Disease Models, Animal; Flow cytometry; Gastrointestinal Tract - pathology; Health aspects; Helper cells; Immunology; Immunoregulation; Inflammation; Inflammation - metabolism; Inflammation Mediators - metabolism; Inflammatory diseases; Interleukin 17; Interleukins; Laboratory animals; Lymphocytes; Lymphocytes T; Medical schools; Mice; Mice, Inbred BALB C; Microscopy; Necrosis; Pathogenesis; PIAS3; Protein Inhibitors of Activated STAT - metabolism; Proteins; Regulatory T cell; Retirement benefits; Rheumatic diseases; Signal Transduction; Spine; Spleen - pathology; Spondylarthritis - immunology; Spondylarthritis - metabolism; Spondyloarthritis; STAT3; Stat3 protein; STAT3 Transcription Factor - metabolism; T cells; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; TNF inhibitors; Transcription; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; Type 17 helper T cell
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-019-1774-x

Spondyloarthritis (SpA) is chronic inflammatory arthritis, and interleukin (IL)-17 is crucial in SpA pathogenesis. Type 17 helper T (Th17) cells are one of major IL-17-secreting cells. Signal transducer and activator of transcription (STAT)-3 signaling induces Th17 differentiation. This study investigated the effects of protein inhibitor of activated STAT3 (PIAS3) on SpA pathogenesis. Curdlan was injected into SKG ZAP-70 mice for SpA induction. The PIAS3 or Mock vector was inserted into mice for 10 weeks. Clinical and histologic scores of the paw, spine, and gut were evaluated. The expression of IL-17, tumor necrosis factor-α (TNF-α), STAT3, and bone morphogenic protein (BMP) was measured. Confocal microscopy and flow cytometry were used to assess Th cell differentiation. PIAS3 significantly diminished the histologic scores of the paw and gut. PIAS3-treated mice displayed decreased expression of IL-17, TNF-α, and STAT3 in the paw, spine, and gut. BMP-2/4 expression was lower in the spines of PIAS3-treated mice. Th cell differentiation was polarized toward the upregulation of regulatory T cells (Tregs) and the downregulation of Th17 in PIAS3-treated mice. PIAS3 had beneficial effects in mice with SpA by reducing peripheral arthritis and gut inflammation. Pro-inflammatory cytokines and Th17/Treg differentiation were controlled by PIAS3. In addition, BMPs were decreased in the spines of PIAS3-treated mice. These findings suggest that PIAS3 could have therapeutic benefits in patients with SpA.