Abstract

Females show a 2- to 10-fold higher incidence of autoimmune diseases compared to males, indicating a role for sex hormones. In this study, we determined the role of progesterone (P) in modulating male and female rodent dendritic cell (DC) responses. We found differences both in male and female DC responses to P and differences in DC responses throughout the female estrus cycle. Male LPS-matured bone marrow-derived DCs (BMDCs) secreted higher levels of TNF-? and IL-10 compared to females; however P suppressed BMDC TNF-? and IL-12 secretion in females more than males. Reversal by the PR antagonist RU486 indicated mediation through PR. Females also showed greater progesterone downregulation of BMDC CD80 and MHC Class II expression than males. Female BMDCs differed in P responsiveness depending on the estrus cycle phase, with similar responses to males in proestrus and estrus but greater sensitivity to P during metaestrus and diestrus. This effect is consistent with increased levels of PR in BMDCs during these phases. Thus, depending on estrus cycle phase and gender, P differentially affects mature BMDC function. This could indicate that differences in susceptibility to infection and disease between males and females and at specific estrus cycle phases in females could be related to differential BMDC function.

This work was supported by the NIMH and NIAID Intramural Research Programs.

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