Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation
Crotonoside, 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 crotono...
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MDPI AG
2020-11-01
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| Series: | Plants |
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| Online Access: | https://www.mdpi.com/2223-7747/9/11/1535 |
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| author | Shih-Chao Lin Chi-Chien Lin Shiming Li Wan-Yi Lin Caitlin W. Lehman Nicole R. Bracci Sen-Wei Tsai |
| author_facet | Shih-Chao Lin Chi-Chien Lin Shiming Li Wan-Yi Lin Caitlin W. Lehman Nicole R. Bracci Sen-Wei Tsai |
| author_sort | Shih-Chao Lin |
| collection | DOAJ |
| description | Crotonoside, 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. |
| first_indexed | 2024-03-10T14:58:09Z |
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| publishDate | 2020-11-01 |
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| series | Plants |
| spelling | doaj.art-ae324a4ce78e4636bdc6a63e743651582023-11-20T20:28:17ZengMDPI AGPlants2223-77472020-11-01911153510.3390/plants9111535Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and ActivationShih-Chao Lin0Chi-Chien Lin1Shiming Li2Wan-Yi Lin3Caitlin W. Lehman4Nicole R. Bracci5Sen-Wei Tsai6Bachelor Degree Program in Marine Biotechnology, National Taiwan Ocean University, Keelung 202301, TaiwanInstitute of Biomedical Science, The iEGG and Animal Biotechnology Center, National Chung-Hsing University, Taichung 402204, TaiwanHubei Key Laboratory for Processing and Application of Catalytic Materials, College of Chemistry and Chemical Engineering, Huanggang Normal University, Hubei 438000, ChinaInstitute of Biomedical Science, The iEGG and Animal Biotechnology Center, National Chung-Hsing University, Taichung 402204, TaiwanDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24063, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24063, USADepartment of Physical Medicine and Rehabilitation, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, TaiwanCrotonoside, 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.https://www.mdpi.com/2223-7747/9/11/1535crotonosiderheumatoid arthritisdendritic cellsdifferentiation |
| spellingShingle | Shih-Chao Lin Chi-Chien Lin Shiming Li Wan-Yi Lin Caitlin W. Lehman Nicole R. Bracci Sen-Wei Tsai Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation Plants crotonoside rheumatoid arthritis dendritic cells differentiation |
| title | Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation |
| title_full | Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation |
| title_fullStr | Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation |
| title_full_unstemmed | Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation |
| title_short | Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation |
| title_sort | alleviation of collagen induced arthritis by crotonoside through modulation of dendritic cell differentiation and activation |
| topic | crotonoside rheumatoid arthritis dendritic cells differentiation |
| url | https://www.mdpi.com/2223-7747/9/11/1535 |
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