Perivascular fibroblasts at the nexus of CNS immunity

Fibroblasts in the central nervous system (CNS) are restricted to the organ's borders, providing mechanical protection, barrier functions, and an infrastructure for the pervading vasculature. An immunological function for these cells has not been considered until recently. In the last decade, new insights into CNS immune surveillance, lymphatic drainage, and the formation of perivascular, lymphoid-like structures have prompted the reevaluation of CNS fibroblast immunobiology. In particular, fibroblasts within the meninges and Virchow-Robin spaces create immune-competent niches, providing cytokines, chemokines, survival factors, and extracellular matrix scaffolds to coordinate local immune cell recruitment, retention, and activation. Except for the peripheral dural meningeal layer, the induction of such immunological programs is absent in the healthy CNS and restricted to pathological conditions. Here, we review recent findings detailing the immunological functions of brain perivascular fibroblasts in the steady state and following a spectrum of pathological perturbations.