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

**Authors:** Yubao Hou, Jianwei Wu, Shuo Yang, Hongwei Wang, Xianghe Wang, Zian Lu, Zhenhao Chen, Jing Feng, Hongli Wang

PMC · DOI: 10.1038/s41413-026-00508-6 · 2026-03-05

## TL;DR

This review explores the newly discovered spinal lymphatic system and its role in fluid balance, immunity, and disease, suggesting new therapeutic possibilities.

## Contribution

The paper introduces the spinal lymphatic system as a novel anatomical pathway linking CNS and vertebral health.

## Key findings

- Spinal lymphatic vessels regulate cerebrospinal fluid drainage and tissue homeostasis.
- Dysfunction in spinal lymphatics is linked to neurological disorders and vertebral degeneration.
- The spinal lymphatic system may serve as a new target for therapeutic interventions.

## 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.

## Full-text entities

- **Genes:** VEGFC (vascular endothelial growth factor C) [NCBI Gene 7424] {aka Flt4-L, LMPH1D, LMPHM4, VRP}, PROX1 (prospero homeobox 1) [NCBI Gene 5629], Cxcl12 (C-X-C motif chemokine ligand 12) [NCBI Gene 20315] {aka Pbsf, Scyb12, Sdf1, Tlsf, Tpar1}, LYVE1 (lymphatic vessel endothelial hyaluronan receptor 1) [NCBI Gene 10894] {aka CRSBP-1, HAR, LYVE-1, XLKD1}, FLT4 (fms related receptor tyrosine kinase 4) [NCBI Gene 2324] {aka CHTD7, FLT-4, FLT41, LMPH1A, LMPHM1, PCL}, Ccr7 (C-C motif chemokine receptor 7) [NCBI Gene 12775] {aka CC-CKR-7, CCR-7, CD197, Cdw197, Cmkbr7, EBI1}, Pecam1 (platelet/endothelial cell adhesion molecule 1) [NCBI Gene 18613] {aka Cd31, PECAM-1, Pecam}, Lyve1 (lymphatic vessel endothelial hyaluronan receptor 1) [NCBI Gene 114332] {aka 1200012G08Rik, Crsbp-1, Lyve-1, Xlkd1}, Pdpn (podoplanin) [NCBI Gene 14726] {aka E11, Gp38, OTS-8, RANDAM-2, T1-alpha, T1a}, Myh11 (myosin, heavy polypeptide 11, smooth muscle) [NCBI Gene 17880] {aka SM1, SM2, smMHC}, Vegfc (vascular endothelial growth factor C) [NCBI Gene 22341] {aka VEGF-C}, Flt4 (FMS-like tyrosine kinase 4) [NCBI Gene 14257] {aka Chy, Flt-4, VEGFR-3, VEGFR3}, H2 (histocompatibility-2, MHC) [NCBI Gene 111364] {aka H-2, MHC-II}, Alad (aminolevulinate, delta-, dehydratase) [NCBI Gene 17025] {aka ALADH, Lv}, Kdr (kinase insert domain protein receptor) [NCBI Gene 16542] {aka 6130401C07, Flk-1, Flk1, Krd-1, Ly73, VEGFR-2}, Prox1 (prospero homeobox 1) [NCBI Gene 19130] {aka A230003G05Rik, PROX-1}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Aqp4 (aquaporin 4) [NCBI Gene 11829] {aka WCH4}, lec (laryngotracheo esophageal cleft) [NCBI Gene 16839], Mbp (myelin basic protein) [NCBI Gene 17196] {aka Hmbpr, golli-mbp, jve, mld, shi}
- **Diseases:** SAH (MESH:D013345), middle cerebral artery occlusion (MESH:D020244), meningiomas (MESH:D008579), autoimmune demyelinating disorder (MESH:D003711), neurological damage (MESH:D020196), rheumatoid arthritis (MESH:D001172), platelet thrombosis (MESH:D013927), metastasis (MESH:D009362), dizziness (MESH:D004244), osteolysis (MESH:D010014), bone loss (MESH:D001847), CNS tumors (MESH:D016543), Hirayama disease (MESH:C538253), spinal lymphangiomas (MESH:D008202), Gorham-Stout disease (MESH:D010015), venous dilation (MESH:D002311), cardiovascular disease (MESH:D002318), Dementia (MESH:D003704), dysfunction (MESH:D006331), glaucoma (MESH:D005901), neuropathic pain (MESH:D009437), infarct (MESH:D007238), AF (OMIM:614822), disc degeneration (MESH:D055959), EAE (MESH:D004681), vertebral degeneration (MESH:D009410), neurological and musculoskeletal disorders (MESH:D009140), CLNs (MESH:D000072717), cognitive decline (MESH:D003072), myelin damage (MESH:D020279), IVD degeneration (MESH:C538167), MS (MESH:D009103), Parkinson's disease (MESH:D010300), fracture (MESH:D050723), pain (MESH:D010146), fibrosis (MESH:D005355), glioma (MESH:D005910), Neurodegenerative disorders (MESH:D019636), venous reflux (MESH:D005764), inflammatory demyelination (MESH:D020277), chronic inflammation (MESH:D007249), CNS (MESH:D002493), edema (MESH:D004487), neuroinflammation (MESH:D000090862), cervical spondylosis (MESH:D055009), Lumbar spinal stenosis (MESH:C563613), Spinal stenosis (MESH:D013130), lymphatic insufficiency (MESH:D000309), cancer (MESH:D009369), Alzheimer's disease (MESH:D000544), neurotoxic (MESH:D020258), Stroke (MESH:D020521), spondyloarthritis (MESH:D013167), venous congestion (MESH:D006940), autoimmune (MESH:D001327), hemorrhage (MESH:D006470), neurological diseases (MESH:D020271), obesity (MESH:D009765), LV (MESH:D018487), LPT (MESH:D008206)
- **Chemicals:** melatonin (MESH:D008550), Indian ink (-), lipids (MESH:D008055), 4-hydroxytamoxifen (MESH:C016601), LPC (MESH:D008244), Visudyne (MESH:D000077362), carbon (MESH:D002244), tamoxifen (MESH:D013629)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Canis lupus familiaris (dog, subspecies) [taxon 9615], Mus musculus (house mouse, species) [taxon 10090]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960967/full.md

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Source: https://tomesphere.com/paper/PMC12960967