Lymphatic-immune interactions in the musculoskeletal system

Abstract

Traditionally, the role of lymphatic vessels has been understood as primarily involving fluid transport and immune surveillance. In addition to these roles, recent studies have revealed a paracrine function of lymphatics through the dissemination of inductive factors, known as lymphangiocrine signals including in musculoskeletal physiology and diseases. These signals play diverse roles, including maintaining tissue equilibrium and facilitating regeneration. Impaired lymphangiocrine signaling and lymphatic function are features of musculoskeletal diseases. This review summarizes dysregulation of lymphatic vessels and interactions with immune cells during musculoskeletal diseases. Further, this review provides insights into lymphangiocrine signals as a potential therapeutic target.

Keywords: aging; bone; immune; lymphatics; musculoskeletal.

Figure 1

Lymphatic vessels in various organs. VEGF-C, Vascular Endothelial Growth Factor - C; VEGFR-3, Vascular Endothelial Growth Factor Receptor-3.

Figure 2

Lymphangiocrine signaling in the musculoskeletal system. CXCL12, C-X-C Motif Chemokine Ligand 12; DAMP, Damage- Associated Molecular Patterns; HSC, Hematopoietic Stem Cells; IL-6, Interleukin 6; M-CSF, Macrophage Colony Stimulating Factor; Sem3a, Semaphorin-3a.

Figure 3

Lymphangiocrine signaling in various diseases. CCL2, C-C Motif Ligand 2; CXCL12, C-X-C Motif Chemokine Ligand 12; CXCL13, C-X-C Motif Chemokine Ligand 13; CXCL21, C-X-C Motif Chemokine Ligand 21; iNOS, Induced Nitric Oxide Synthase; INSL6, Insulin Like 6; M-SCF, Macrophage Colony Stimulating Factor; MMPs, Matrix Metalloproteinases; OA, Osteoarthritis; RA, Rheumatoid Arthritis; Sem3a, Semaphorin-3a; TNF, Tumor Necrosis Factor; VEGF-C, Vascular Endothelial Growth Factor -C; ILs, Inflammatory Factors.