The spinal lymphatic system: an emerging pathway bridging fluid homeostasis, immunity, and disease

Abstract

The lymphatic system, traditionally regarded as a unidirectional conduit for interstitial fluid and immune cell transport, has recently been redefined through the discovery of lymphatic networks along the spinal axis. These spinal lymphatic vessels, encompassing the spinal cord, vertebral bones, and intervertebral discs, challenge long-standing anatomical dogmas and introduce new perspectives on the interplay between the central nervous system (CNS) and the vertebral column. This review systematically summarizes the distribution and dual functions of the spinal lymphatic system in regulating cerebrospinal fluid drainage, maintaining tissue homeostasis, and mediating immune responses. Furthermore, we highlight emerging evidence linking spinal lymphatic dysfunction to spinal pathologies, neurological disorders, and vertebral degeneration. Based on these findings, we propose that the spinal lymphatic system constitutes a previously underappreciated pathway integrating spinal cord and vertebral physiology, with potential implications for both disease progression and therapeutic intervention. While research on the cranial lymphatic system has rapidly advanced, the spinal lymphatic system remains comparatively underexplored. We hope this review will catalyze further investigation into spinal lymphatic biology and inform the development of novel therapeutic strategies targeting spinal and neurological diseases.

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Funding

National Key Research and Development Program of China (grant no. 2024YFC3505305) Shanghai Municipal Natural Science Foundation (grant no. 23ZR1474500) the Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDB1060000)

National Natural Science Foundation of China (National Science Foundation of China)(82571383)

National Key Research and Development Program of China (grant no. 2024YFC3505305), Shanghai Municipal Natural Science Foundation (grant no. 23ZR1474500), the Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDB1060000), State Key Laboratory of Chemical Biology (grant No. SKLCB-2025-02),2024 Shanghai Oriental Talent Program Youth Project (DFYCQN04),2025 The "Clinical Famous Doctor Cultivation Project" of Shanghai Medical College, Fudan University (DGF828030-1/005)

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The Author(s)