The primary cilium as a compartmentalized signaling hub in tissue immunity and homeostasis

Abstract

Cilia are evolutionarily conserved microtubule-based organelles that function as sensory and motile hubs central to mucosal immunity and systemic immune homeostasis. Motile cilia drive mucociliary clearance as a primary physical defense; meanwhile primary cilia function as signaling scaffolds that regulate immune receptor dynamics including PD-L1 trafficking. These organelles also modulate inflammatory responses through pathways such as cGAS-STING. Disruptions in ciliary assembly, intraflagellar transport, or signaling drive pathological immune dysregulation, contributing to viral infections, chronic inflammatory diseases, and ciliopathy-related immune dysfunction. This review summarizes core ciliary signaling pathways and their roles in host defense and immune homeostasis, integrating recent advances linking ciliary defects to diverse immune-related pathologies. We discuss current limitations in understanding ciliary immunobiology and propose key directions for future research aimed at deepening mechanistic insights and facilitating clinical translation.