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调控记忆T淋巴细胞促炎的分子网络
2020-03-17 21:37

2020年3月16日出版的《自然-免疫学》杂志在线发表了瑞士提契诺大学Silvia Monticelli研究组的最新成果,他们发现了调控人类记忆T淋巴细胞促炎的分子网络。

为了确定影响T细胞致病性的分子决定因素,研究人员基于离体原代记忆T淋巴细胞可产生高水平炎症细胞因子的特点,对其进行了分离。研究发现,记忆性T淋巴细胞产生炎性细胞因子的表型是由特定核心基因标志决定的,并受NF-κB途径组成性激活和转录阻遏物BHLHE40表达的调控。BHLHE40减弱了抗炎因子的表达,包括miR-146a(NF-κB活化的负调控因子)和ZC3H12D(Regnase-1家族的RNase,能够降解炎性转录本)的负调节因子。该研究数据揭示了调控人类记忆T淋巴细胞促炎的分子网络,并且其可能促进疾病发生。

研究人员表示,了解调控辅助性T淋巴细胞功能的机制对于破解人类正常和病原性免疫反应至关重要。

附:英文原文

Title: A molecular network regulating the proinflammatory phenotype of human memory T lymphocytes

Author: Stefan Emming, Niccol Bianchi, Sara Polletti, Chiara Balestrieri, Cristina Leoni, Sara Montagner, Michele Chirichella, Nicolas Delaleu, Gioacchino Natoli, Silvia Monticelli

Issue&Volume: 2020-03-16

Abstract: Understanding the mechanisms that modulate helper T lymphocyte functions is crucial to decipher normal and pathogenic immune responses in humans. To identify molecular determinants influencing the pathogenicity of T cells, we separated ex vivo-isolated primary human memory T lymphocytes on the basis of their ability to produce high levels of inflammatory cytokines. We found that the inflammatory, cytokine-producing phenotype of memory T lymphocytes was defined by a specific core gene signature and was mechanistically regulated by the constitutive activation of the NF-κB pathway and by the expression of the transcriptional repressor BHLHE40. BHLHE40 attenuated the expression of anti-inflammatory factors, including miR-146a, a negative regulator of NF-κB activation and ZC3H12D, an RNase of the Regnase-1 family able to degrade inflammatory transcripts. Our data reveal a molecular network regulating the proinflammatory phenotype of human memory T lymphocytes, with the potential to contribute to disease.

DOI: 10.1038/s41590-020-0622-8

Source: https://www.nature.com/articles/s41590-020-0622-8

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:31.25
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

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