Testosterone acts directly on CD4+ T lymphocytes to increase IL-10 production

Area of Science:

• Immunology
• Endocrinology

Background:

• Males show lower susceptibility to autoimmune diseases like experimental autoimmune encephalomyelitis compared to females.
• Gender disparities in cytokine production by splenocytes may explain these differences in disease susceptibility.

Purpose of the Study:

• To investigate gender differences in cytokine production upon stimulation with antibody to CD3 (Ab to CD3).
• To elucidate the mechanisms underlying testosterone's influence on immune responses and IL-10 production.

Main Methods:

• Compared cytokine production (IL-10, IL-4, IL-12) in splenocytes from male and female mice stimulated with Ab to CD3.
• Administered dihydrotestosterone (DHT) to female mice and analyzed cytokine profiles.
• Utilized IL-12 knockout mice to differentiate direct vs. indirect effects of testosterone.
• Determined the cellular source of IL-10 and assessed androgen receptor expression on CD4+ T lymphocytes.
• Conducted in vitro experiments treating CD4+ T lymphocytes with DHT.

Main Results:

• Male splenocytes produced more IL-10 and IL-4, and less IL-12 than female splenocytes after Ab to CD3 stimulation.
• DHT treatment in female mice increased IL-10 and decreased IL-12 production, without affecting IL-4.
• DHT treatment increased IL-10 production in female IL-12 knockout mice, supporting a direct effect of testosterone.
• IL-10 was primarily produced by CD4+ T lymphocytes, which express androgen receptors.
• In vitro DHT treatment of CD4+ T lymphocytes enhanced IL-10 production.

Conclusions:

• Testosterone directly acts on CD4+ T lymphocytes via androgen receptors to increase IL-10 gene expression.
• These findings suggest a mechanism for testosterone's immunomodulatory effects and potential role in sex-based differences in autoimmune diseases.