Meningeal IL-17 producing T cells mediate cognitive impairment in salt-sensitive hypertension
Santisteban, M. M.; Faraco, G.; Brea Lopez, D.; Wang, G.; Sobanko, M. J.; Sciortino, R.; Racchumi, G.; Waisman, A.; Anrather, J.; Iadecola, C.
Show abstract
Hypertension, a disease afflicting over one billion individuals worldwide, is a leading cause of cognitive impairment, the mechanisms of which remain poorly understood. In a mouse model of hypertension, we found that the neurovascular and cognitive dysfunction depends on IL-17, a cytokine elevated in hypertensive individuals. However, neither circulating IL-17 or brain angiotensin signaling could account in full for the dysfunction. Rather, IL-17 produced by T-cells in the dura mater was the major culprit by reaching the cerebrospinal fluid and activating IL-17 receptors on brain associated macrophages. Accordingly, depleting brain macrophages, deleting IL17-RA in brain macrophages, or suppressing meningeal T cells completely rescued cognitive function without attenuating blood pressure elevation, circulating IL-17 or brain angiotensin signaling. The data unveil a critical role of meningeal T-cells and macrophage IL-17 signaling in the neurovascular and cognitive dysfunction of hypertension and suggest novel therapies to counteract the devastating effects of hypertension on cognitive health.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Elevated pyramidal cell firing orchestrates arteriolar vasoconstriction through COX-2-derived prostaglandin E2 signaling 95%
- Endothelial Pannexin 1-TRPV4 channel signaling lowers pulmonary arterial pressure 94%
- An antisense oligonucleotide-based strategy to ameliorate cognitive dysfunction in the 22q11.2 Deletion Syndrome 94%
Similar papers in this journal
Similar papers in this journal
- Neural stem and progenitor cells support and protect adult hippocampal function via vascular endothelial growth factor secretion. 96%
- Serotonin sensing by microglia conditions the proper development of neuronal circuits and of social and adaptive skills 94%
- AIM2 Inflammasome Mediates Hallmark Neuropathological Alterations and Cognitive Impairment in a Mouse Model of Vascular Dementia 94%
Similar papers in this journal
- Neutrophil-microglia interaction drives reversible motor dysfunction in neuromyelitis optica model induced by subarachnoid AQP4-IgG 95%
- The human glucocorticoid receptor variant rs6190 promotes blood cholesterol and atherosclerosis 94%
- Hyperactive GluN2B impairs neuroplasticity and cognition in phenylketonuria 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.