Human pDCs display sex-specific differences in type I interferon subtypes and interferon α/β receptor expression

Area of Science:

• Immunology
• Sex Differences in Immunity
• Infectious and Autoimmune Diseases

Background:

• Disease outcomes often differ between sexes, with women more susceptible to autoimmune and certain infectious diseases.
• Plasmacytoid dendritic cells (pDCs) are key producers of interferon-alpha (IFN-α) upon toll-like receptor 7 (TLR7) stimulation, potentially explaining sex-based immune variations.

Purpose of the Study:

• To investigate sex-specific differences in type I interferon (IFN-I) induction in pDCs following TLR7 stimulation.
• To explore the molecular mechanisms underlying sex-based disparities in IFN-I production.

Main Methods:

• Isolated human pDCs were stimulated with TLR7 agonists.
• mRNA expression levels of all 13 IFN-α subtypes and IFN-β were quantified.
• Surface expression of the common IFN-α/β receptor subunit 2 was analyzed.

Main Results:

• pDCs from females exhibited significantly higher mRNA expression for all 13 IFN-α subtypes compared to males.
• Female pDCs also showed increased IFN-β mRNA levels after TLR7 stimulation.
• Higher surface expression of IFN-α/β receptor 2 was observed on female pDCs.

Conclusions:

• Sex-specific differences in IFN-I production by pDCs are evident at the mRNA level upon TLR7 stimulation.
• Elevated IFN-α/β receptor 2 expression on female pDCs may contribute to heightened IFN-I responses.
• These findings offer insights into sex-based immunological differences relevant to disease pathogenesis.