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树突状表皮细胞在皮肤癌中的作用。

Role of Dendritic Epidermal T Cells in Cutaneous Carcinoma.

机构信息

Department of Microbiology and Immunology, School of Medicine, Jinan University, Guangzhou, China.

出版信息

Front Immunol. 2020 Jul 14;11:1266. doi: 10.3389/fimmu.2020.01266. eCollection 2020.

Abstract

Dendritic epidermal T cells (DETCs) are γδ T cells expressing invariant Vγ5Vδ1 T cell receptor (TCR) in murine epidermis. Initially, the development and the maturation of DETC progenitors are mediated by skint-1, TCR, and cytokines in the fetal thymus. Then, the DETC progenitors migrate to the epidermis with the guidance of selectins, CCR10, CCR4, . Eventually, mature DETCs proliferate and maintain a homeostatic population in the epidermis through IL-15 and aryl hydro-carbon receptor signaling. In "stressed" skin, DETCs are activated, exhibiting features such as a round morphology, cytotoxicity, and production of cytokines. In cutaneous carcinoma, DETCs generally inhibit tumor development directly in non-major histocompatibility complex-restricted manner, with the assistance of cytokines. DETCs also recognize and inhibit tumor via TCR, non-TCR receptors (such as 2B4 and NKG2D), or both. This study summarizes the biogenesis and the function of DETCs in cutaneous carcinoma and clarifies the essential surveillance role in the epidermis that DETCs play. As there are no DETCs in human epidermis but only human epidermis γδ T cells, we need to understand the anti-tumor pathways used by DETCs to find analogous immune pathways in human skin, which could be exploited for novel therapeutics.

摘要

树突状表皮 T 细胞 (DETC) 是在鼠类表皮中表达不变的 Vγ5Vδ1 T 细胞受体 (TCR) 的 γδ T 细胞。最初,DETC 前体的发育和成熟是由胎儿胸腺中的 skint-1、TCR 和细胞因子介导的。然后,DETC 前体在选择素、CCR10、CCR4 的引导下迁移到表皮。最终,成熟的 DETCs 通过 IL-15 和芳香烃受体信号增殖并维持表皮中的稳态群体。在“应激”皮肤中,DETCs 被激活,表现出圆形形态、细胞毒性和细胞因子产生等特征。在皮肤癌中,DETCs 通常以非主要组织相容性复合体限制的方式直接抑制肿瘤的发展,这得益于细胞因子的辅助。DETCs 还通过 TCR、非 TCR 受体(如 2B4 和 NKG2D)或两者兼而有之来识别和抑制肿瘤。本研究总结了 DETCs 在皮肤癌中的发生和功能,并阐明了 DETCs 在表皮中发挥的基本监视作用。由于人类表皮中没有 DETCs,只有人类表皮 γδ T 细胞,我们需要了解 DETCs 用于抗肿瘤的途径,以在人类皮肤中找到类似的免疫途径,从而为新的治疗方法提供依据。

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本文引用的文献

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The Dynamics of the Skin's Immune System.皮肤免疫系统的动态。
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Front Immunol. 2018 May 14;9:1059. doi: 10.3389/fimmu.2018.01059. eCollection 2018.
4
Recasting Human Vδ1 Lymphocytes in an Adaptive Role.重塑人类 Vδ1 淋巴细胞的适应性作用。
Trends Immunol. 2018 Jun;39(6):446-459. doi: 10.1016/j.it.2018.03.003. Epub 2018 Apr 18.
7
Histologic Mimics of Basal Cell Carcinoma.基底细胞癌的组织学模仿物
Arch Pathol Lab Med. 2017 Nov;141(11):1490-1502. doi: 10.5858/arpa.2017-0222-RA.

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