| Autor: |
Marie Marotel, Marine Villard, Annabelle Drouillard, Issam Tout, Laurie Besson, Omran Allatif, Marine Pujol, Yamila Rocca, Michelle Ainouze, Guillaume Roblot, Sébastien Viel, Melissa Gomez, Veronique Loustaud, Sophie Alain, David Durantel, Thierry Walzer, Uzma Hasan, Antoine Marçais |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 10 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.60095 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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