Calvarial bone channels and a putative craniomaxillary–brain interface in central nervous system immunity
image: Figure 1: Calvarial SBCs undergo developmental remodeling, are influenced by myeloid and osteoclast-associated pathways involving RANKL and TRPV4, and modulate immune-cell movement from skull marrow to the meninges during neuroinflammation. Solid elements represent findings supported by calvarial studies, whereas dashed elements indicate hypothetical craniomaxillary extensions that require experimental validation.
Credit: Ziwen Sheng, Yulong Zhang, Hao Wang, Wenyu Zhen, Youming Zhu*, Haitao Wang*, Hengguo Zhang*
Skull bone marrow has recently been recognized as an important local cellular reservoir involved in immune regulation at central nervous system (CNS) borders. Through skull bone channels (SBCs), it can directly communicate with the meninges, providing a local route for immune-cell trafficking between skull marrow and meningeal compartments. Recent studies further show that SBCs exhibit marked developmental plasticity, are regulated by RANKL-, osteoclast-, and TRPV4-associated mechanisms, and influence meningeal immune-cell infiltration during neuroinflammation. Building on this established skull marrow–meninges axis, this article proposes a “putative craniomaxillary–brain interface” to explore whether oral and craniofacial tissues may participate in CNS-border immune regulation. The framework considers three non-mutually exclusive routes: a putative local osseous or vascular route between craniomaxillary marrow and CNS-border compartments, a trigeminal neuroimmune route driven by inflammatory signals from dental pulp and periodontal tissues, and a systemic inflammatory route involving oral microbial products, cytokines, and circulating myeloid cells. The article further discusses oral-specific factors, including periodontitis, dental pulp inflammation, and masticatory and orthodontic mechanical loading, and their potential to influence craniofacial marrow immune niches through RANKL/TRPV4-associated bone remodeling. It also summarizes approaches for testing this hypothesis, including high-resolution 3D imaging, spatial molecular profiling, and source-specific cell tracing, and discusses the potential translational value of skull marrow routes for CNS drug delivery and disease intervention. Importantly, there is currently no direct evidence that maxillary or mandibular marrow delivers immune cells to the meninges through SBC-like structures. The putative craniomaxillary–brain interface should therefore be regarded not as an established immune pathway, but as a conceptual framework requiring further validation through anatomical tracing, source-to-destination cell tracking, and relevant disease models.