Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation

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dc.contributor.authorLin, Shih-Chaoen
dc.contributor.authorLin, Chi-Chienen
dc.contributor.authorLi, Shimingen
dc.contributor.authorLin, Wan-Yien
dc.contributor.authorLehman, Caitlin W.en
dc.contributor.authorBracci, Nicole R.en
dc.contributor.authorTsai, Sen-Weien
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2020-11-12T17:23:34Zen
dc.date.available2020-11-12T17:23:34Zen
dc.date.issued2020-11-10en
dc.date.updated2020-11-12T14:15:01Zen
dc.description.abstractCrotonoside, a guanosine analog originally isolated from <i>Croton tiglium</i>, is reported to be a potent tyrosine kinase inhibitor with immunosuppressive effects on immune cells. Due to its potential immunotherapeutic effects, we aimed to evaluate the anti-arthritic activity of crotonoside and explore its immunomodulatory properties in alleviating the severity of arthritic symptoms. To this end, we implemented the treatment of crotonoside on collagen-induced arthritic (CIA) DBA/1 mice and investigated its underlying mechanisms towards pathogenic dendritic cells (DCs). Our results suggest that crotonoside treatment remarkably improved clinical arthritic symptoms in this CIA mouse model as indicated by decreased pro-inflammatory cytokine production in the serum and suppressed expression of co-stimulatory molecules, CD40, CD80, and MHC class II, on CD11c<sup>+</sup> DCs from the CIA mouse spleens. Additionally, crotonoside treatment significantly reduced the infiltration of CD11c<sup>+</sup> DCs into the synovial tissues. Our in vitro study further demonstrated that bone marrow-derived DCs (BMDCs) exhibited lower yield in numbers and expressed lower levels of CD40, CD80, and MHC-II when incubated with crotonoside. Furthermore, LPS-stimulated mature DCs exhibited limited capability to prime antigen-specific CD4<sup>+</sup> and T-cell proliferation, cytokine secretions, and co-stimulatory molecule expressions when treated with crotonoside. Our pioneer study highlights the immunotherapeutic role of crotonoside in the alleviation of the CIA via modulation of pathogenic DCs, thus creating possible applications of crotonoside as an immunosuppressive agent that could be utilized and further explored in treating autoimmune disorders in the future.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLin, S.-C.; Lin, C.-C.; Li, S.; Lin, W.-Y.; Lehman, C.W.; Bracci, N.R.; Tsai, S.-W. Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation. Plants 2020, 9, 1535.en
dc.identifier.doihttps://doi.org/10.3390/plants9111535en
dc.identifier.urihttp://hdl.handle.net/10919/100849en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectcrotonosideen
dc.subjectrheumatoid arthritisen
dc.subjectdendritic cellsen
dc.subjectdifferentiationen
dc.titleAlleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activationen
dc.title.serialPlantsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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