Altered memory CCR6

CCR6 DNA damage DNA repair HIV infection HIV persistence Th17 cells Transcriptomics

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
22 Aug 2024
Historique:
received: 30 01 2024
revised: 17 07 2024
accepted: 27 07 2024
medline: 24 8 2024
pubmed: 24 8 2024
entrez: 23 8 2024
Statut: aheadofprint

Résumé

Despite successful antiretroviral therapy (ART), frequencies and immunological functions of memory CCR6 mRNA-sequencing was performed using Illumina technology on freshly FACS-sorted memory CCR6 Decreased Th17 cell frequencies in STs and ECs versus HDs coincided with reduced Th17-lineage cytokine production in vitro. Accordingly, the RORγt/RORC2 repressor NR1D1 was upregulated, while the RORγt/RORC2 inducer Semaphorin 4D was decreased in memory CCR6 These results reveal new molecular mechanisms of Th17 cell deficit in ST and EC PWH despite a successful control of HIV-1 replication. This knowledge points to potential therapeutic interventions to limit HIV-1 infection and restore frequencies, effector functions, and senescence/exhaustion in Th17 cells. This study was funded by the Canadian Institutes of Health Research (CIHR, operating grant MOP 142294, and the Canadian HIV Cure Enterprise [CanCURE 2.0] Team Grant HB2 164064), and in part, by the Réseau SIDA et maladies infectieuses du Fonds de recherche du Québec-Santé (FRQ-S).

Sections du résumé

BACKGROUND BACKGROUND
Despite successful antiretroviral therapy (ART), frequencies and immunological functions of memory CCR6
METHODS METHODS
mRNA-sequencing was performed using Illumina technology on freshly FACS-sorted memory CCR6
FINDINGS RESULTS
Decreased Th17 cell frequencies in STs and ECs versus HDs coincided with reduced Th17-lineage cytokine production in vitro. Accordingly, the RORγt/RORC2 repressor NR1D1 was upregulated, while the RORγt/RORC2 inducer Semaphorin 4D was decreased in memory CCR6
INTERPRETATION CONCLUSIONS
These results reveal new molecular mechanisms of Th17 cell deficit in ST and EC PWH despite a successful control of HIV-1 replication. This knowledge points to potential therapeutic interventions to limit HIV-1 infection and restore frequencies, effector functions, and senescence/exhaustion in Th17 cells.
FUNDING BACKGROUND
This study was funded by the Canadian Institutes of Health Research (CIHR, operating grant MOP 142294, and the Canadian HIV Cure Enterprise [CanCURE 2.0] Team Grant HB2 164064), and in part, by the Réseau SIDA et maladies infectieuses du Fonds de recherche du Québec-Santé (FRQ-S).

Identifiants

DOI: 10.1016/j.ebiom.2024.105274 PMID: 39178742
pubmed: 39178742
pii: S2352-3964(24)00310-4
doi: 10.1016/j.ebiom.2024.105274
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

105274

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests We have no competing interest to declare.

Auteurs

Alexis Yero (A)

Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal (UQAM), Montreal, QC, Canada.

Jean-Philippe Goulet (JP)

CellCarta, Montreal, QC, Canada.

Tao Shi (T)

Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal (UQAM), Montreal, QC, Canada.

Cecilia T Costiniuk (CT)

Chronic Viral Illness Service and Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Jean-Pierre Routy (JP)

Chronic Viral Illness Service and Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Cecile Tremblay (C)

Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montreal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montreal, QC, Canada.

Ralph-Sydney Mboumba Bouassa (RS)

Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal (UQAM), Montreal, QC, Canada.

Yulia Alexandrova (Y)

Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal (UQAM), Montreal, QC, Canada.

Amélie Pagliuzza (A)

Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montreal, QC, Canada.

Nicolas Chomont (N)

Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montreal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montreal, QC, Canada.

Petronela Ancuta (P)

Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montreal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montreal, QC, Canada.

Mohammad-Ali Jenabian (MA)

Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal (UQAM), Montreal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montreal, QC, Canada. Electronic address: jenabian.mohammad-ali@uqam.ca.

Classifications MeSH