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
Abstract Background 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 differentiatio...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-01-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-019-1774-x |
| _version_ | 1819085643919130624 |
|---|---|
| author | Hong-Ki Min JeongWon Choi Seon-Yeong Lee Hyeon-Beom Seo KyungAh Jung Hyun Sik Na Jun-Geol Ryu Seung-Ki Kwok Mi-La Cho Sung-Hwan Park |
| author_facet | Hong-Ki Min JeongWon Choi Seon-Yeong Lee Hyeon-Beom Seo KyungAh Jung Hyun Sik Na Jun-Geol Ryu Seung-Ki Kwok Mi-La Cho Sung-Hwan Park |
| author_sort | Hong-Ki Min |
| collection | DOAJ |
| description | Abstract Background 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-70W163C mice for SpA induction. Methods 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. Results 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. Conclusion 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. |
| first_indexed | 2024-12-21T21:07:37Z |
| format | Article |
| id | doaj.art-c490c1cc2d544eccb74d76144492c12b |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-21T21:07:37Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-c490c1cc2d544eccb74d76144492c12b2022-12-21T18:50:14ZengBMCJournal of Translational Medicine1479-58762019-01-011711910.1186/s12967-019-1774-xProtein 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 spondyloarthritisHong-Ki Min0JeongWon Choi1Seon-Yeong Lee2Hyeon-Beom Seo3KyungAh Jung4Hyun Sik Na5Jun-Geol Ryu6Seung-Ki Kwok7Mi-La Cho8Sung-Hwan Park9Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of KoreaRheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of KoreaImpact BiotechRheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of KoreaDivision of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of KoreaRheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of KoreaDivision of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of KoreaAbstract Background 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-70W163C mice for SpA induction. Methods 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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s12967-019-1774-xSpondyloarthritisPIAS3Type 17 helper T cellRegulatory T cell |
| spellingShingle | Hong-Ki Min JeongWon Choi Seon-Yeong Lee Hyeon-Beom Seo KyungAh Jung Hyun Sik Na Jun-Geol Ryu Seung-Ki Kwok Mi-La Cho Sung-Hwan Park 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 Journal of Translational Medicine Spondyloarthritis PIAS3 Type 17 helper T cell Regulatory T cell |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Spondyloarthritis PIAS3 Type 17 helper T cell Regulatory T cell |
| url | http://link.springer.com/article/10.1186/s12967-019-1774-x |
| work_keys_str_mv | AT hongkimin proteininhibitorofactivatedstat3reducesperipheralarthritisandgutinflammationandregulatestheth17tregcellimbalanceviastat3signalinginamousemodelofspondyloarthritis AT jeongwonchoi proteininhibitorofactivatedstat3reducesperipheralarthritisandgutinflammationandregulatestheth17tregcellimbalanceviastat3signalinginamousemodelofspondyloarthritis AT seonyeonglee proteininhibitorofactivatedstat3reducesperipheralarthritisandgutinflammationandregulatestheth17tregcellimbalanceviastat3signalinginamousemodelofspondyloarthritis AT hyeonbeomseo proteininhibitorofactivatedstat3reducesperipheralarthritisandgutinflammationandregulatestheth17tregcellimbalanceviastat3signalinginamousemodelofspondyloarthritis AT kyungahjung proteininhibitorofactivatedstat3reducesperipheralarthritisandgutinflammationandregulatestheth17tregcellimbalanceviastat3signalinginamousemodelofspondyloarthritis AT hyunsikna proteininhibitorofactivatedstat3reducesperipheralarthritisandgutinflammationandregulatestheth17tregcellimbalanceviastat3signalinginamousemodelofspondyloarthritis AT jungeolryu proteininhibitorofactivatedstat3reducesperipheralarthritisandgutinflammationandregulatestheth17tregcellimbalanceviastat3signalinginamousemodelofspondyloarthritis AT seungkikwok proteininhibitorofactivatedstat3reducesperipheralarthritisandgutinflammationandregulatestheth17tregcellimbalanceviastat3signalinginamousemodelofspondyloarthritis AT milacho proteininhibitorofactivatedstat3reducesperipheralarthritisandgutinflammationandregulatestheth17tregcellimbalanceviastat3signalinginamousemodelofspondyloarthritis AT sunghwanpark proteininhibitorofactivatedstat3reducesperipheralarthritisandgutinflammationandregulatestheth17tregcellimbalanceviastat3signalinginamousemodelofspondyloarthritis |