Neuroimmune interactions in sleep regulation: Epigenetic interfaces between microglia and T cells in brain homeostasis and dysfunction

Sleep serves as a fundamental regulator of brain functions, integrating processes of neuroplasticity, metabolic homeostasis, and immune surveillance. Among the diverse immune constituents implicated in these dynamics, microglia and T cells have emerged as pivotal effectors, whose activities are finely tuned to sleep-wake rhythms. These cell populations exert significant regulatory influence over neuronal excitability, synaptic integrity, and behavioral expression. Their functional states are governed by intrinsic circadian mechanisms as well as extrinsic environmental cues, while their transcriptional and phenotypic landscapes are modulated by epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs. Perturbations in sleep architecture due to chronic sleep deprivation, circadian disruption or neuroinflammatory conditions can induce epigenetic reprogramming in both microglia and T cells leading to aberrant immune activation, defective synaptic maintenance, and cognitive impairment. This review synthesizes emerging evidence that delineates the intricate connections between sleep dynamics and the epigenetic regulation of neuroimmune function, with particular emphasis on the coordinated roles of microglia and T cells in maintaining central nervous system (CNS) homeostasis. A deeper mechanistic understanding of these regulatory networks is indispensable for developing targeted therapeutic interventions that modulate neuroimmune interactions in sleep-associated neurological and psychiatric disorders.