CCR3 plays a role in murine age-related cognitive changes and T-cell infiltration into the brain
Sanket Rege, Arnaud Teichert, Juliet Masumi, Onkar S. Dhande, Reema Harish, Brett W. Higgins, Yesenia Lopez, Lily Akrapongpisak, Hannah Hackbart, Sofia Caryotakis, Dino P. Leone, Balázs Szőke, Jonas Hannestad, Karoly Nikolich, Steven P. Braithwaite, Sakura Minami
Abstract
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.