Diabetic Stroke Promotes a Sexually Dimorphic Expansion of T Cells
We recently reported that diabetes negates the cerebrovascular protection typically seen in adult female rats resulting in cognitive impairment, which is worsened by increased parenchymal bleeding and edema after ischemic stroke. Although women experience more severe diabetes and suffer from a higher rate of diabetic complications, including stroke and cognitive impairment, underlying mechanisms contributing to sex differences are limited. Emerging evidence suggests interleukin (IL)-17 contributes to cerebrovascular pathologies: (1) high salt diet-mediated expansion of IL-17-producing T cells (Th17) in the gut microbiome promotes cerebrovascular dysfunction and cognitive impairment in male mice, (2) increased IL-17-producing γδTCR cells exacerbates stroke injury in male mice, and (3) IL-17 promotes rupture of cerebral aneurysms in female mice. Based on these premises, we investigated the potential involvement of IL-17-producing inflammatory cells in cerebrovascular dysfunction and post-stroke vascular injury in diabetes by measuring intestinal, circulating, or cerebral T cell profiles as well as in plasma IL-17 in both sexes. Cell suspensions prepared from naive or stroked (3 days after stroke) diabetic and control rats were analyzed by flow cytometry, and IL-17 levels were measured in plasma using ELISA. Diabetes deferentially promoted the expansion of cerebral Th17 cells in females. In response to stroke, diabetes had a sexually dimorphic effect on the expansion of numerous T cell profiles. These results suggest that a better understanding of the role of IL-17-producing cells in diabetes may identify potential avenues in which the molecular mechanisms contributing to these sex differences can be further elucidated.
KeywordsDiabetes Stroke IL-17 Female Brain Blood
This study was supported by Veterans Affairs (VA) Merit Review (BX000347), VA Senior Research Career Scientist Award, National Institute of Health (NIH) R01NS083559 and R01 NS104573 (multi-PI, Susan C. Fagan as co-PI) to Adviye Ergul; a TL1 Award TL1 TR002382 and UL1TR002378 to Ladonya Jackson; and Diabetic Complications Research Consortium DiaComp Awards 17AU3831/18AU3903 (DK076169/115255) to Dr. Weiguo Li.
Compliance with Ethical Standards
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
All rats were housed in the animal care facility at Augusta University, which is approved by the American Association for Accreditation of Laboratory Animal Care. All experiments were conducted in accordance with the National Institute of Health (NIH) guidelines for the care and use of animals in research. Furthermore, all protocols were approved by the institutional animal care and use committee.
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