Fig. 1: Timeline understanding of neuroimmune interactions.

Since the neuroimmune system entered the immune interaction stage, it has undergone three milestone phases. The following three figures illustrate these phases: A The discovery of immune cells in the dura mater has reshaped our understanding of meningeal immunity and demonstrated its crucial role in guiding and coordinating CNS immunity. This discovery marked the beginning of the neuroimmune system’s transition into the immune interaction stage. B The identification of functional lymphatic vessels in the dura mater sinus challenged the traditional view that the CNS lacks lymphatic vessels. This finding has provided new insights into the pathways for immune cell and metabolic waste clearance within the CNS and has shed light on the development of neurodegenerative diseases. C The discovery of SMCs has advanced the understanding of neuroimmune interactions to a new level. It has highlighted the significance of bone marrow hematopoiesis in the skull and refined the analysis of the origin, distribution, function, and heterogeneity of immune cells in both the meninges and brain parenchyma under homeostatic and various pathological conditions.