Mobilization of lymphatic endothelial precursor cells and lymphatic neovascularization in primary Sjögren's syndrome
Copyright policy )Mobilization of lymphatic endothelial precursor cells and lymphatic neovascularization in primary Sjögren's syndrome
AbstractAlthough lymphatic neovascularization may be a key feature of chronic inflammation, it is almost unexplored in primary Sjögren's syndrome (pSS). A recent study revealed a pro‐lymphangiogenic function of interleukin (IL)‐17, a leading player in pSS pathogenesis. The aims of the study were to investigate lymphangiogenic mediators and lymphatic vasculature in pSS, as well as their possible association with IL‐17. Circulating lymphatic endothelial precursor cells (LEPCs) and Th17 cells were enumerated in pSS patients and healthy donors. VEGF‐C and IL‐17 levels were assessed in paired serum samples. Lymphatic vasculature, VEGF‐C/VEGF receptor (VEGFR)‐3 and IL‐17 were evaluated in pSS minor salivary glands (MSGs) and compared with normal and non‐specific chronic sialadenitis (NSCS) MSGs. Circulating LEPCs were expanded in pSS and correlated with circulating Th17 cells, IL‐17 and VEGF‐C. In pSS MSGs, a newly formed lymphatic capillary network was found within periductal inflammatory infiltrates and the number of interlobular lymphatic vessels was significantly increased compared with normal and NSCS MSGs. Strong VEGF‐C expression was detected in pSS ductal epithelial cells and periductal inflammatory cells. Numerous VEGFR‐3+ infiltrating mononuclear cells were exclusively observed in pSS MSGs. VEGFR‐3 expression was strongly increased in lymphatic capillaries of pSS MSGs. IL‐17+ inflammatory cells were preferentially observed around lymphatic vessels in pSS MSGs. This study supports the notion that lymphvasculogenesis and lymphangiogenesis are active in pSS, thereby unmasking a novel aspect of disease pathogenesis. In addition, our results suggest another possible pathogenic role of IL‐17 in pSS, further supporting its therapeutic targeting in this disease.
- Università degli studi di Salerno Italy
- University of Florence Italy
- University of Perugia Italy
Male, Vascular Endothelial Growth Factor C, Salivary Glands, Minor, Sialadenitis, Diagnosis, Differential, Humans, Lymphangiogenesis, Lymphatic Vessels, IL-17; Th17 cells; lymphangiogenesis; lymphatic endothelial precursor cells; lymphvasculogenesis; minor salivary glands; primary Sjögren's syndrome, Neovascularization, Pathologic, Interleukin-17, Endothelial Cells, Original Articles, Middle Aged, Vascular Endothelial Growth Factor Receptor-3, IL-17; Lymphangiogenesis; Lymphatic endothelial precursor cells; Lymphvasculogenesis; Minor salivary glands; Primary Sjögren's syndrome; Th17 cells; Case-Control Studies; Diagnosis, Differential; Endothelial Cells; Female; Gene Expression Regulation; Humans; Interleukin-17; Lymphangiogenesis; Lymphatic Vessels; Male; Middle Aged; Neovascularization, Pathologic; Salivary Glands, Minor; Sialadenitis; Signal Transduction; Sjogren's Syndrome; Th17 Cells; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-3; Molecular Medicine; Cell Biology, Sjogren's Syndrome, Gene Expression Regulation, Case-Control Studies, Th17 Cells, Female, Signal Transduction
Male, Vascular Endothelial Growth Factor C, Salivary Glands, Minor, Sialadenitis, Diagnosis, Differential, Humans, Lymphangiogenesis, Lymphatic Vessels, IL-17; Th17 cells; lymphangiogenesis; lymphatic endothelial precursor cells; lymphvasculogenesis; minor salivary glands; primary Sjögren's syndrome, Neovascularization, Pathologic, Interleukin-17, Endothelial Cells, Original Articles, Middle Aged, Vascular Endothelial Growth Factor Receptor-3, IL-17; Lymphangiogenesis; Lymphatic endothelial precursor cells; Lymphvasculogenesis; Minor salivary glands; Primary Sjögren's syndrome; Th17 cells; Case-Control Studies; Diagnosis, Differential; Endothelial Cells; Female; Gene Expression Regulation; Humans; Interleukin-17; Lymphangiogenesis; Lymphatic Vessels; Male; Middle Aged; Neovascularization, Pathologic; Salivary Glands, Minor; Sialadenitis; Signal Transduction; Sjogren's Syndrome; Th17 Cells; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-3; Molecular Medicine; Cell Biology, Sjogren's Syndrome, Gene Expression Regulation, Case-Control Studies, Th17 Cells, Female, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).23 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!