Excess BAFF Alters NR4As Expression Levels and Breg Function of Human Precursor-like Marginal Zone B-Cells in the Context of HIV-1 Infection.
BAFF
Breg
HIV
MZp
NR4A
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
01 Dec 2022
01 Dec 2022
Historique:
received:
09
11
2022
revised:
24
11
2022
accepted:
29
11
2022
entrez:
11
12
2022
pubmed:
12
12
2022
medline:
15
12
2022
Statut:
epublish
Résumé
We have reported excess B-cell activating factor (BAFF) in the blood of HIV-infected progressors, which was concomitant with increased frequencies of precursor-like marginal zone (MZp) B-cells, early on and despite antiretroviral therapy (ART). In controls, MZp possess a strong B-cell regulatory (Breg) potential. They highly express IL-10, the orphan nuclear receptors (NR)4A1, NR4A2 and NR4A3, as well as the ectonucleotidases CD39 and CD73, all of which are associated with the regulation of inflammation. Furthermore, we have shown MZp regulatory function to involve CD83 signaling. To address the impact of HIV infection and excessive BAFF on MZp Breg capacities, we have performed transcriptomic analyses by RNA-seq of sorted MZp B-cells from the blood of HIV-infected progressors. The Breg profile and function of blood MZp B-cells from HIV-infected progressors were assessed by flow-cytometry and light microscopy high-content screening (HCS) analyses, respectively. We report significant downregulation of NR4A1, NR4A2, NR4A3 and CD83 gene transcripts in blood MZp B-cells from HIV-infected progressors when compared to controls. NR4A1, NR4A3 and CD83 protein expression levels and Breg function were also downregulated in blood MZp B-cells from HIV-infected progressors and not restored by ART. Moreover, we observe decreased expression levels of NR4A1, NR4A3, CD83 and IL-10 by blood and tonsillar MZp B-cells from controls following culture with excess BAFF, which significantly diminished their regulatory function. These findings, made on a limited number of individuals, suggest that excess BAFF contributes to the alteration of the Breg potential of MZp B-cells during HIV infection and possibly in other situations where BAFF is found in excess.
Identifiants
pubmed: 36499469
pii: ijms232315142
doi: 10.3390/ijms232315142
pmc: PMC9741410
pii:
doi:
Substances chimiques
B-Cell Activating Factor
0
Interleukin-10
130068-27-8
Orphan Nuclear Receptors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CIHR
ID : PJT-148529
Pays : Canada
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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