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.

Autor: Beisel, Claudia, Jordan-Paiz, Ana, Köllmann, Sandra, Ahrenstorf, Annika Elise, Padoan, Benedetta, Barkhausen, Tanja, Addo, Marylyn M., Altfeld, Marcus
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Zdroj: Biology of Sex Differences; 2/22/2023, Vol. 14 Issue 1, p1-11, 11p
Abstrakt: 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. Highlights: Women showed higher percentage of IRF5 positive B cells compared to men. After stimulation with a TLR7 or TLR9 agonist, women showed higher percentages of IRF5 positive B cells compared with those of men. B cells of women produced higher levels of TNF-α in response to TLR9 stimulation. IRF5 represents a potential therapeutic target to reduce harmful B cell-mediated immune responses in women. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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