Peripheral immune influences on the brain: adaptive immune T and B cells regulate cognitive dysfunction

Abstract

Abstract Cognitive dysfunction is recognized as one of the most concerning complications in aging as well as in disease states such as neurodegenerative disorders and stroke. Although previous studies mainly focused on local brain pathology, growing evidence highlights neuroimmune crosstalk as a key regulator of cognitive function. In particular, bidirectional communication between peripheral adaptive immunity and the central nervous system (CNS) has emerged as an important mechanism underlying cognitive dysfunction. T- and B-cell subsets exert distinct effects on cognitive regulation, ranging from maintaining homeostasis to driving neuroinflammation and dysfunction. Following blood-brain barrier disruption, peripheral lymphocytes infiltrate the CNS and reshape the neuroinflammatory microenvironment through interactions with distinct glial cells. In parallel, meningeal immunity and lymphatic drainage have been identified as critical interfaces linking peripheral and central immune responses in cognitive regulation. In this review, we summarize the multifaceted roles of adaptive immune T and B cells in cognitive dysfunction, with particular emphasis on their subset-specific features, their crosstalk with glial cells, and the contribution of meningeal immunity. We further discuss the potential underlying mechanisms, with the aim of providing insights that may inform therapeutic strategies for cognitive dysfunction.