Peripheral natural killer cells in chronic hepatitis B patients display multiple molecular features of T cell exhaustion.
calcium pathway
dysfunction
human
immunology
inflammation
mTOR
natural killer
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
28 01 2021
28 01 2021
Historique:
received:
16
06
2020
accepted:
28
01
2021
pubmed:
29
1
2021
medline:
4
2
2022
entrez:
28
1
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33507150
doi: 10.7554/eLife.60095
pii: 60095
pmc: PMC7870135
doi:
pii:
Substances chimiques
Antiviral Restriction Factors
0
Banques de données
GEO
['GSE153946']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021, Marotel et al.
Déclaration de conflit d'intérêts
MM, MV, AD, IT, LB, OA, MP, YR, MA, GR, SV, MG, VL, SA, DD, TW, UH, AM No competing interests declared
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