Research PaperSex differences in regulatory cells in experimental stroke

- Female mice with MCAO had smaller infarcts than males.
- In brain, MCAO females had more Bregs and anti-inflammatory macrophages than males.
- In spleen, females had higher total cell numbers but fewer B10 Bregs than males.
- Increased immunosuppressive activity in brain accounts for milder stroke in females.
- Sex-dependent differences in immune regulation affect stroke treatments.

Stroke is the leading cause of disability in the United States. Sex differences, including smaller infarcts in females and greater involvement of immune-mediated inflammation in males may affect the efficacy of immune-modulating interventions. To address these differences, we sought to identify distinct stroke-modifying mechanisms in female vs. male mice. The current study demonstrated smaller infarcts and increased levels of regulatory CD19+CD5+CD1dhi B10 cells as well as anti-inflammatory CD11b+CD206+ microglia/macrophages in the ipsilateral vs. contralateral hemisphere of female but not male mice undergoing 60 min middle cerebral artery occlusion followed by 96 h of reperfusion. Moreover, female mice with MCAO had increased total spleen cell numbers but lower B10 levels in spleens. These results elucidate differing sex-dependent regulatory mechanisms that account for diminished stroke severity in females and underscore the need to test immune-modulating therapies for stroke in both males and females.