IL-19 Is a Novel Lymphangiocrine Factor Inducing Lymphangiogenesis and Lymphatic Junctional Regulation

Area of Science:

• Immunology
• Vascular Biology
• Cell Biology

Background:

• The lymphatic system is crucial for tissue homeostasis, relying on specific junctional protein complexes for proper function.
• Inflammation disrupts lymphatic vessel junctional morphology, leading to malfunction.
• The impact of immunomodulatory cytokines on lymphatic vessel formation and function during inflammation is not well understood.

Purpose of the Study:

• To investigate the role of Interleukin-19 (IL-19) in lymphangiogenesis (lymphatic vessel formation) and lymphatic function during inflammation.
• To test the hypothesis that IL-19 promotes lymphatic vessel formation and function in inflammatory conditions.

Main Methods:

• Utilized cultured human dermal lymphatic endothelial cells to assess IL-19 expression and lymphangiogenesis.
• Employed immunocytochemistry and electric cell-substrate impedance sensing to analyze junctional morphology and permeability in vitro.
• Conducted RNA sequencing to determine IL-19's effects on gene expression.
• Used Il19/Ldlr double knockout mice to evaluate IL-19's in vivo effects on lymphatic function and vessel visualization.

Main Results:

• IL-19 is lymphangiogenic, enhancing human dermal lymphatic endothelial cell migration, network formation, and proliferation.
• IL-19 influences the expression of transcription factors and permeability-associated genes, including VE-cadherin phosphorylation, increasing endothelial cell monolayer permeability.
• In vivo, Il19/Ldlr knockout mice exhibited impaired lymphatic drainage and reduced lymphatic branching, with a higher proportion of zippered junctions.

Conclusions:

• IL-19 demonstrates significant effects on lymphatic vessel formation and function both in vitro and in vivo.
• IL-19 plays a regulatory role in lymphatic drainage.
• IL-19 emerges as a potential immunomodulatory cytokine for therapeutic intervention in cases of inflammation-induced lymphatic dysfunction.