CCR3 plays a role in murine age-related cognitive changes and T-cell infiltration into the brain.
Sanket V RegeArnaud TeichertJuliet MasumiOnkar S DhandeReema HarishBrett W HigginsYesenia LopezLily AkrapongpisakHannah HackbartSofia CaryotakisDino P LeoneBalazs SzokeJonas HannestadKaroly NikolichSteven P BraithwaiteS Sakura MinamiPublished in: Communications biology (2023)
Targeting immune-mediated, age-related, biology has the potential to be a transformative therapeutic strategy. However, the redundant nature of the multiple cytokines that change with aging requires identification of a master downstream regulator to successfully exert therapeutic efficacy. Here, we discovered CCR3 as a prime candidate, and inhibition of CCR3 has pro-cognitive benefits in mice, but these benefits are not driven by an obvious direct action on central nervous system (CNS)-resident cells. Instead, CCR3-expressing T cells in the periphery that are modulated in aging inhibit infiltration of these T cells across the blood-brain barrier and reduce neuroinflammation. The axis of CCR3-expressing T cells influencing crosstalk from periphery to brain provides a therapeutically tractable link. These findings indicate the broad therapeutic potential of CCR3 inhibition in a spectrum of neuroinflammatory diseases of aging.
Keyphrases
- dendritic cells
- regulatory t cells
- induced apoptosis
- white matter
- traumatic brain injury
- adipose tissue
- transcription factor
- cell cycle arrest
- blood brain barrier
- climate change
- cancer therapy
- inflammatory response
- cognitive impairment
- cerebrospinal fluid
- high fat diet induced
- lps induced
- subarachnoid hemorrhage
- emergency medicine