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

TY - JOUR

T1 - 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

AU - Beisel, Claudia

AU - Jordan-Paiz, Ana

AU - Köllmann, Sandra

AU - Ahrenstorf, Annika Elise

AU - Padoan, Benedetta

AU - Barkhausen, Tanja

AU - Addo, Marylyn M

AU - Altfeld, Marcus

N1 - © 2023. The Author(s).

PY - 2023/2/22

Y1 - 2023/2/22

N2 - 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.

AB - 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.

KW - Female

KW - Humans

KW - Male

KW - Cytokines/metabolism

KW - Interferon Regulatory Factors/metabolism

KW - Sex Characteristics

KW - Toll-Like Receptor 7/metabolism

KW - Toll-Like Receptor 9/metabolism

KW - Tumor Necrosis Factor-alpha/metabolism

KW - B-Lymphocytes/metabolism

U2 - 10.1186/s13293-023-00495-x

DO - 10.1186/s13293-023-00495-x

M3 - SCORING: Journal article

C2 - 36814288

VL - 14

SP - 11

JO - BIOL SEX DIFFER

JF - BIOL SEX DIFFER

SN - 2042-6410

IS - 1

ER -