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一种新型的人角质形成细胞与 T 细胞之间的非接触通讯:角质形成细胞衍生的外泌体支持超抗原诱导的静止 T 细胞增殖。

A novel non‑contact communication between human keratinocytes and T cells: Exosomes derived from keratinocytes support superantigen‑induced proliferation of resting T cells.

机构信息

Department of Dermatology and Rheumatology Immunology, Xinqiao Hospital, Third Military Medical University, Chongqing 400000, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):7032-7038. doi: 10.3892/mmr.2017.7492. Epub 2017 Sep 13.

Abstract

It is widely accepted that keratinocytes act as non‑professional antigen‑presenting cells and support superantigen‑induced proliferation of resting T cells; however, it remains unknown whether keratinocytes function in situ with T cells via a non‑contact mechanism. The current study used a transwell co‑culture system and demonstrated, for the first time to the best of the authors' knowledge, that HaCaT cells (the human keratinocyte cell line) did induce T cell proliferation via indirect contact. The data further indicated that exosomes, small membrane vesicles that transfer antigens to recipient cells, are also involved in the superantigen‑associated immunity of keratinocytes. The current study provided experimental evidence that HaCaT‑exosomes contained MHC I and II, and could interact with T cells. In addition, following interferon γ stimulation, Staphylococcal aureus enterotoxin B‑loaded HaCaT cells secreted exosomes to induce the proliferation of CD4+ and CD8+ T cells in vitro. This novel biological function of exosomes reveals a new mechanism of how keratinocytes participate in bacterial superantigen‑induced immune responses.

摘要

人们普遍认为角质形成细胞作为非专业的抗原提呈细胞,支持超抗原诱导静止 T 细胞的增殖;然而,角质形成细胞是否通过非接触机制与 T 细胞在原位发挥作用仍不清楚。本研究使用 Transwell 共培养系统,首次在作者所知的范围内证明,HaCaT 细胞(人角质形成细胞系)确实通过间接接触诱导 T 细胞增殖。数据进一步表明,外泌体是一种将抗原转移到受体细胞的小膜囊泡,也参与了角质形成细胞的超抗原相关免疫。本研究提供了实验证据表明,HaCaT 来源的外泌体含有 MHC I 和 II,并且可以与 T 细胞相互作用。此外,在干扰素 γ 刺激后,金黄色葡萄球菌肠毒素 B 负载的 HaCaT 细胞分泌外泌体,在体外诱导 CD4+和 CD8+T 细胞的增殖。外泌体的这种新的生物学功能揭示了角质形成细胞参与细菌超抗原诱导的免疫反应的新机制。

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