A Designed alpha-GalCer Analog Promotes Considerable Th1 Cytokine Response by Activating the CD1d-iNKT Axis and CD11b-Positive Monocytes/Macrophages
文献类型：期刊论文
| 作者 | Ma, Juan; He, Peng; Zhao, Chuanfang; Ren, Quanzhong; Dong, Zheng; Qiu, Jiahuang; Jing, Yang; Liu, Sijin; Du, Yuguo |
| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 2020-07 |
| 卷号 | 7期号:14页码:1-9 |
| 关键词 | antitumor activity CD11b monocytes CD1d Th1-biased immune responses alpha-GalCer analogs |
| 英文摘要 | Selective helper T cell 1 (Th1) priming agonists are a promising area of investigation for immunotherapeutic treatment of various diseases. alpha-galactosylceramide (alpha-GalCer, KRN7000), a well-studied Th1-polarizer, simultaneously induces helper T cell 2 (Th2)-type responses, which is a major drawback for its clinical applications. Based on surflex-docking computation, alpha-GalCer-diol, with added hydroxyl groups in the acyl chain, is designed and synthesized. Structural analyses reveal stronger affinity between alpha-GalCer-diol and cluster of differentiation 1d (CD1d), leading to enhanced antigen presentation by dendritic cells (DCs) and self-activation, as reflected by tight binding of the T-cell receptor (TCR)/KRN7000/CD1d ternary complex and elevated production of interleukin 12 (IL-12) and interferon-gamma (IFN-gamma). Consequently, invariant natural killer T cells (iNKTs) are activated and exhibit an improved Th1-type cytokine profile ex vivo and in vivo. Different from KRN7000, alpha-GalCer-diol markedly boosts the expansion of the CD11b(+) subpopulation and enhances IFN-gamma content in CD11b(+) cells. These reinforced Th1-type responses collectively endow alpha-GalCer-diol more robust antitumor activity in a xenograft animal model using B16-F10 melanoma cells. Together, the data demonstrate a new mechanism through which alpha-GalCer-diol induces stronger Th1-type responses by stimulating CD11b(+) leukocyte expansion and DC-conducted CD1d-restricted and TCR-mediated iNKT activation. Hence, this study may facilitate the development of novel Th1 priming agonists. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/44576]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Ma, Juan,He, Peng,Zhao, Chuanfang,et al. A Designed alpha-GalCer Analog Promotes Considerable Th1 Cytokine Response by Activating the CD1d-iNKT Axis and CD11b-Positive Monocytes/Macrophages[J]. ADVANCED SCIENCE,2020,7(14):1-9. |
| APA | Ma, Juan.,He, Peng.,Zhao, Chuanfang.,Ren, Quanzhong.,Dong, Zheng.,...&Du, Yuguo.(2020).A Designed alpha-GalCer Analog Promotes Considerable Th1 Cytokine Response by Activating the CD1d-iNKT Axis and CD11b-Positive Monocytes/Macrophages.ADVANCED SCIENCE,7(14),1-9. |
| MLA | Ma, Juan,et al."A Designed alpha-GalCer Analog Promotes Considerable Th1 Cytokine Response by Activating the CD1d-iNKT Axis and CD11b-Positive Monocytes/Macrophages".ADVANCED SCIENCE 7.14(2020):1-9. |
入库方式： OAI收割
来源：生态环境研究中心
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