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Dynamics and epigenetic signature of regulatory T-cells following antiretroviral therapy initiation in acute HIV infection
- Source :
- EBioMedicine, Vol 71, Iss, Pp 103570-(2021), EBioMedicine
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Background HIV infection promotes the expansion of immunosuppressive regulatory T-cells (Tregs), contributing to immune dysfunction, tissue fibrosis and disease progression. Early antiretroviral treatment (ART) upon HIV infection improves CD4 count and decreases immune activation. However, Treg dynamics and their epigenetic regulation following early ART initiation remain understudied. Methods Treg subsets were characterized by flow cytometry in 103 individuals, including untreated HIV-infected participants in acute and chronic phases, ART-treated in early infection, elite controllers (ECs), immunological controllers (ICs), and HIV-uninfected controls. The methylation status of six regulatory regions of the foxp3 gene was assessed using MiSeq technology. Findings Total Treg frequency increased overtime during HIV infection, which was normalized in early ART recipients. Tregs in untreated individuals expressed higher levels of activation and immunosuppressive markers (CD39, and LAP(TGF-β1)), which remained unchanged following early ART. Expression of gut migration markers (CCR9, Integrin-β7) by Tregs was elevated during untreated HIV infection, while they declined with the duration of ART but not upon early ART initiation. Notably, gut-homing Tregs expressing LAP(TGF-β1) and CD39 remained higher despite early treatment. Additionally, the increase in LAP(TGF-β1)+ Tregs overtime were consistent with higher demethylation of conserved non-coding sequence (CNS)-1 in the foxp3 gene. Remarkably, LAP(TGF-β1)-expressing Tregs in ECs were significantly higher than in uninfected subjects, while the markers of Treg activation and gut migration were not different. Interpretation Early ART initiation was unable to control the levels of immunosuppressive Treg subsets and their gut migration potential, which could ultimately contribute to gut tissue fibrosis and HIV disease progression. Funding This study was funded by the Canadian Institutes of Health Research (CIHR, grant MOP 142294) and in part by the AIDS and Infectious Diseases Network of the Reseau SIDA et maladies infectieuses du Fonds de recherche du Quebec-Sante (FRQ-S).
- Subjects :
- Male
Medicine (General)
Research paper
Integrin beta Chains
CCR9
HIV Infections
antiretroviral therapy (ART)
T-Lymphocytes, Regulatory
Epigenesis, Genetic
0302 clinical medicine
Transforming Growth Factor beta
TGF-β1
Medicine
Sida
0303 health sciences
medicine.diagnostic_test
biology
Apyrase
FOXP3
Forkhead Transcription Factors
General Medicine
Methylation
3. Good health
Regulatory sequence
Female
Adult
Anti-HIV Agents
chemical and pharmacologic phenomena
General Biochemistry, Genetics and Molecular Biology
Flow cytometry
Receptors, CCR
03 medical and health sciences
R5-920
Acquired immunodeficiency syndrome (AIDS)
Antigens, CD
FoxP3
Humans
Epigenetics
030304 developmental biology
CD39
business.industry
regulatory T-cells (Tregs)
HIV
DNA Methylation
medicine.disease
biology.organism_classification
Immunology
business
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 23523964
- Volume :
- 71
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....382ddc7404bbea4747d1d7e19dc58cef