| Title: |
Peripheral natural killer cells in chronic hepatitis B patients display multiple molecular features of T cell exhaustion |
| Authors: |
Marotel, Marie; Villard, Marine; Drouillard, Annabelle; Tout, Issam; Besson, Laurie; Allatif, Omran; Pujol, Marine; Rocca, Yamila; Ainouze, Michelle; Roblot, Guillaume; Viel, Sébastien; Gomez, Melissa; Loustaud, Veronique; Alain, Sophie; Durantel, David; Walzer, Thierry; Hasan, Uzma; Marçais, Antoine |
| Contributors: |
Centre International de Recherche en Infectiologie (CIRI); École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Activation et transduction du signal dans les lymphocytes - Lymphocyte activation and signaling CIRI (CIRI-LYACTS); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon); Service d’Immunologie biologique, Hôpital Lyon Sud, Hospices Civils de Lyon, Lyon, France; BioInformatique et BioStatistiques CIRI (CIRI-BIBS); Hospices Civils de Lyon (HCL); Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT); CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST); Université de Limoges (UNILIM)-Université de Limoges (UNILIM); Centre Hospitalier Universitaire Dupuytren 1 et 2 (CHU Limoges); CHU Limoges; Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL); Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Interactions entre HBV, HDV, et des facteurs hépatiques de l'hôte CIRI (CIRI-HepVIR); Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy CIRI (CIRI-EVIR) |
| Source: |
EISSN: 2050-084X ; eLife ; https://hal.science/hal-04121064 ; eLife, 2021, 10, ⟨10.7554/eLife.60095⟩ |
| Publisher Information: |
CCSD; eLife Sciences Publication |
| Publication Year: |
2021 |
| Collection: |
Université Jean Monnet – Saint-Etienne: HAL |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.7554/eLife.60095 |
| Availability: |
https://hal.science/hal-04121064; https://hal.science/hal-04121064v1/document; https://hal.science/hal-04121064v1/file/Marotel%20M%20eLife%202021.pdf; https://doi.org/10.7554/eLife.60095 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.D76E9065 |
| Database: |
BASE |