慢性乙型肝炎患者外周自然杀伤细胞表现出T细胞衰竭的多种

StephenW

Peripheral Natural Killer cells in chronic hepatitis B patients display multiple molecular features of T cell exhaustion
Marie Marotel  1 , Marine Villard  1 , Annabelle Drouillard  2 , Issam Tout  1 , Laurie Besson  1 , Omran Allatif  2 , Marine Pujol  1 , Yamila Rocca  1 , Michelle Ainouze  1 , Guillaume Roblot  1 , Sébastien Viel  2 , Melissa Gomez  3 , Veronique Loustaud  3 , Sophie Alain  3 , David Durantel  4 , Thierry Walzer  2 , Uzma Hasan  1 , Antoine Marçais  2
Affiliations
Affiliations

    1
    Immunology, Inserm, Lyon, France.
    2
    International Center for Infectiology Research (CIRI), Lyon, France.
    3
    Hepathology, CHU Limoges, Limoges, France.
    4
    Cancerology, Inserm, Lyon, France.

    PMID: 33507150 DOI: 10.7554/eLife.60095

Abstract

Antiviral effectors such as Natural Killer (NK) cells have impaired functions in chronic hepatitis B (CHB) patients. The molecular mechanism responsible for this dysfunction remains poorly characterized. We show that decreased cytokine production capacity of peripheral NK cells from CHB patients was associated with reduced expression of NKp30 and CD16, and defective mTOR pathway activity. Transcriptome analysis of patients NK cells revealed an enrichment for transcripts expressed in exhausted T cells suggesting that NK cell dysfunction and T cell exhaustion employ common mechanisms. In particular, the transcription factor TOX and several of its targets were over-expressed in NK cells of CHB patients. This signature was predicted to be dependent on the calcium-associated transcription factor NFAT. Stimulation of the calcium-dependent pathway recapitulated features of NK cells from CHB patients. Thus, deregulated calcium signalling could be a central event in both T cell exhaustion and NK cell dysfunction occurring during chronic infections.

Keywords: human; immunology; inflammation.

© 2021, Marotel et al.

StephenW

慢性乙型肝炎患者外周自然杀伤细胞表现出T细胞衰竭的多种分子特征
Marie Marotel 1，Marine Villard 1，Annabelle Drouillard 2，Issam Tout 1，Laurie Besson 1，Omran Allatif 2，Marine Pujol 1，Yamila Rocca 1，Michelle Ainouze 1，Guillaume Roblot 1，SébastienViel 2，Melissa Gomez 3，Veronique Loustaud 3，索菲·阿兰3，大卫·杜兰特尔4，蒂埃里·沃尔泽2，乌兹玛·哈桑1，安东尼·马赛2
隶属关系
隶属关系

    1个
    免疫学，Inserm，里昂，法国。
    2
    法国里昂国际传染病研究中心（CIRI）。
    3
    血液学，CHU里摩日，法国里摩日。
    4
    癌症学，Inserm，里昂，法国。

    PMID：33507150 DOI：10.7554 / eLife.60095

抽象

在慢性乙型肝炎（CHB）患者中，诸如自然杀伤（NK）细胞等抗病毒效应子的功能受损。导致这种功能障碍的分子机制仍然很差。我们显示，CHB患者外周血NK细胞的细胞因子生产能力下降与NKp30和CD16的表达减少以及mTOR通路活性降低有关。对患者NK细胞的转录组分析显示，在精疲力竭的T细胞中表达的转录物富集，这表明NK细胞功能障碍和T细胞精疲力竭采用共同的机制。尤其是，转录因子TOX及其几个靶标在CHB患者的NK细胞中过表达。预计该签名依赖于钙相关转录因子NFAT。钙依赖性途径的刺激概括了来自CHB患者的NK细胞的特征。因此，失调的钙信号传导可能是慢性感染过程中T细胞衰竭和NK细胞功能异常的主要事件。

关键词：人免疫学炎。

©2021年，Marotel等。

StephenW

https://elifesciences.org/download/aHR0cHM6Ly9jZG4uZWxpZmVzY2llbmNlcy5vcmcvYXJ0aWNsZXMvNjAwOTUvZWxpZmUtNjAwOTUtdjEucGRmP2Nhbm9uaWNhbFVyaT1odHRwczovL2VsaWZlc2NpZW5jZXMub3JnL2FydGljbGVzLzYwMDk1/elife-60095-v1.pdf?_hash=Ke%2F7N0OXO%2FoSBJUGykKC%2BggLWDwVJU7PpDTi2nLZOkA%3Delife-60095-v1-1.pdf