Sex differences in the percentage of IRF5 positive B cells are associated with higher production of TNF-α in women in response to TLR9 in humans.
B cells
Interferon regulatory factor 5
Sex differences
Toll-like receptor 7/9
Tumor necrosis factor-α
Journal
Biology of sex differences
ISSN: 2042-6410
Titre abrégé: Biol Sex Differ
Pays: England
ID NLM: 101548963
Informations de publication
Date de publication:
22 02 2023
22 02 2023
Historique:
received:
31
10
2022
accepted:
09
02
2023
entrez:
23
2
2023
pubmed:
24
2
2023
medline:
25
2
2023
Statut:
epublish
Résumé
The clinical course and outcome of many diseases differ between women and men, with women experiencing a higher prevalence and more severe pathogenesis of autoimmune diseases. The precise mechanisms underlying these sex differences still remain to be fully understood. IRF5 is a master transcription factor that regulates TLR/MyD88-mediated responses to pathogen-associated molecular patterns (PAMPS) in DCs and B cells. B cells are central effector cells involved in autoimmune diseases via the production of antibodies and pro-inflammatory cytokines as well as mediating T cell help. Dysregulation of IRF5 expression has been reported in autoimmune diseases, including systemic lupus erythematosus, primary Sjögren syndrome, and rheumatoid arthritis. In the current study, we analyzed whether the percentage of IRF5 positive B cells differs between women and men and assessed the resulting consequences for the production of inflammatory cytokines after TLR7- or TLR9 stimulation. The percentage of IRF5 positive B cells was significantly higher in B cells of women compared to men in both unstimulated and TLR7- or TLR9-stimulated B cells. B cells of women produced higher levels of TNF-α in response to TLR9 stimulation. Taken together, our data contribute to the understanding of sex differences in immune responses and may identify IRF5 as a potential therapeutic target to reduce harmful B cell-mediated immune responses in women.
Sections du résumé
BACKGROUND
The clinical course and outcome of many diseases differ between women and men, with women experiencing a higher prevalence and more severe pathogenesis of autoimmune diseases. The precise mechanisms underlying these sex differences still remain to be fully understood. IRF5 is a master transcription factor that regulates TLR/MyD88-mediated responses to pathogen-associated molecular patterns (PAMPS) in DCs and B cells. B cells are central effector cells involved in autoimmune diseases via the production of antibodies and pro-inflammatory cytokines as well as mediating T cell help. Dysregulation of IRF5 expression has been reported in autoimmune diseases, including systemic lupus erythematosus, primary Sjögren syndrome, and rheumatoid arthritis.
METHODS
In the current study, we analyzed whether the percentage of IRF5 positive B cells differs between women and men and assessed the resulting consequences for the production of inflammatory cytokines after TLR7- or TLR9 stimulation.
RESULTS
The percentage of IRF5 positive B cells was significantly higher in B cells of women compared to men in both unstimulated and TLR7- or TLR9-stimulated B cells. B cells of women produced higher levels of TNF-α in response to TLR9 stimulation.
CONCLUSIONS
Taken together, our data contribute to the understanding of sex differences in immune responses and may identify IRF5 as a potential therapeutic target to reduce harmful B cell-mediated immune responses in women.
Identifiants
pubmed: 36814288
doi: 10.1186/s13293-023-00495-x
pii: 10.1186/s13293-023-00495-x
pmc: PMC9945365
doi:
Substances chimiques
Cytokines
0
Interferon Regulatory Factors
0
IRF5 protein, human
0
TLR9 protein, human
0
Toll-Like Receptor 7
0
Toll-Like Receptor 9
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11Subventions
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : DFG RU5068
Informations de copyright
© 2023. The Author(s).
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