Abstract:
:A transplanted organ is usually rejected without any major immunosuppressive treatment because of vigorous alloimmune responsiveness. However, continuous global immunosuppression may cause severe side effects, including nephrotoxicity, tumors, and infections. Therefore, it is necessary to seek novel immunosuppressive agents, especially natural ingredients that may provide sufficient efficacy in immunosuppression with minimal side effects. Shikonin is a bioactive naphthoquinone pigment, an ingredient originally extracted from the root of Lithospermum erythrorhizon. Previous studies have shown that shikonin regulates immunity and exerts anti-inflammatory effects. In particular, it can ameliorate arthritis in animal models. However, it is unclear whether shikonin inhibits alloimmunity or allograft rejection. In this study and for the first time, we demonstrated that shikonin significantly prolonged the survival of skin allografts in wild-type mice. Shikonin increased the frequencies of CD4+Foxp3+ regulatory T cells (Tregs) post-transplantation and induced CD4+Foxp3+ Tregs in vitro as well. Importantly, depleting the Tregs abrogated the extension of skin allograft survival induced by shikonin. It also decreased the frequencies of CD8+CD44highCD62Llow effector T cells and CD11c+CD80+/CD11c+CD86+ mature DCs after transplantation. Moreover, we found that shikonin inhibited the proliferation of T cells in vitro and suppressed their mTOR signaling. It also reduced the gene expression of pro-inflammatory cytokines, including IFNγ, IL-6, TNFα, and IL-17A, while increasing the gene expression of anti-inflammatory mediators IL-10, TGF-β1, and indoleamine-2, 3-dioxygenase (IDO) in skin allografts. Further, shikonin downregulated IDO protein expression in skin allografts and DCs in vitro. Taken together, shikonin inhibits allograft rejection via upregulating CD4+Foxp3+ Tregs. Thus, shikonin is a novel immunosuppressant that could be potentially used in clinical transplantation.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Zeng Q,Qiu F,Chen Y,Liu C,Liu H,Liang CL,Zhang Q,Dai Zdoi
10.3389/fimmu.2019.00652subject
Has Abstractpub_date
2019-04-01 00:00:00pages
652issn
1664-3224journal_volume
10pub_type
杂志文章abstract:BACKGROUND:Subjects are considered infected with Trypanosoma cruzi when tested positive by at least two out of three serological tests, whereas a positive result in only one of up to three tests is termed "serodiscordant" (SD). Assessment of parasite-specific T-cell responses may help discriminate the uninfected from i...
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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更新日期:2020-09-30 00:00:00
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pub_type: 杂志文章,评审
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abstract::[This corrects the article DOI: 10.3389/fimmu.2020.562282.]. ...
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pub_type: 已发布勘误
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更新日期:2020-12-16 00:00:00
abstract::Acute graft-vs.-host disease (GVHD) limits the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT), a main therapy to treat various hematological disorders. Despite rapid progress in understanding GVHD pathogenesis, broad immunosuppressive agents are most often used to prevent and remain the fir...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00309
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2014.00661
更新日期:2015-01-13 00:00:00
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pub_type: 杂志文章
doi:10.3389/fimmu.2019.01243
更新日期:2019-06-04 00:00:00
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pub_type: 杂志文章
doi:10.3389/fimmu.2020.00093
更新日期:2020-01-31 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00352
更新日期:2017-03-27 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01063
更新日期:2019-05-09 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02411
更新日期:2019-10-11 00:00:00
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pub_type: 杂志文章
doi:10.3389/fimmu.2019.00538
更新日期:2019-03-22 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2018-09-27 00:00:00
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更新日期:2020-04-27 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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doi:10.3389/fimmu.2019.01700
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