Peripheral Natural Killer cells in chronic hepatitis B patients display multiple molecular features of T cell exhaustion.

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 characterised. 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.

journal_name

Elife

journal_title

eLife

authors

Marotel M,Villard M,Drouillard A,Tout I,Besson L,Allatif O,Pujol M,Rocca Y,Ainouze M,Roblot G,Viel S,Gomez M,Loustaud V,Alain S,Durantel D,Walzer T,Hasan U,Marçais A

doi

10.7554/eLife.60095

subject

Has Abstract

pub_date

2021-01-28 00:00:00

issn

2050-084X

pii

60095

journal_volume

10

pub_type

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