Androgen receptor signaling protects male mice from the development of immune response to peanut

Peanut (PN) allergy is a major public health concern. Recent research has brought clarity about how individuals become sensitized to PN allergen with routes known through the skin, as well as the airway. Still unclear, however, is the role of sex hormones on the development of allergic immune responses to PN. This study examines the role of androgen receptor (AR) signaling in regulating PN-specific immune responses.

We utilized a 4-week inhalation mouse model of PN allergy that is known to drive the production of PN-specific antibodies and elicit systemic anaphylaxis following PN challenge. Wildtype (WT) male, female, and androgen receptor-deficient testicular feminization mutant (AR^Tfm) male mice were examined using this model to document sex differences in PN allergy. To determine if sex differences also existed in the cellular immune response, this study utilized a 3-day inhalation mouse model of PN to examine the response of group 2 innate lymphoid cells (ILC2s). WT male and female mice were examined using this model to document sex differences in ILC2 response within the lungs.

AR use is critical in regulating PN-specific antibody levels. We found that AR^Tfm males have a higher antibody response and significantly worse anaphylactic response following PN challenge relative to WT males. WT males also exhibit a less severe anaphylactic response compared to AR^Tfm male and female mice. Lastly, we discovered that lung ILC2s from female mice respond more robustly to PN compared to ILC2s within WT male mice.

Taken together, this study suggests that male sex hormones, namely androgens, negatively regulate allergic immune responses to PN.