Paneth Cells Regulate Lymphangiogenesis under Control of Microbial Signals during Experimental Portal Hypertension

Area of Science:

• Gastroenterology
• Vascular Biology
• Microbiology

Background:

• Intestinal microbiota influences portal hypertension via vascular regulation.
• Bacterial antigens activate Paneth cells (PCs) to secrete factors affecting angiogenesis and portal hypertension.
• The role of PCs in regulating lymphatic vessel development under microbiota control during portal hypertension is unexplored.

Purpose of the Study:

• To investigate the role of Paneth cells in regulating intestinal lymphatic vessel development during experimental portal hypertension.
• To determine if Paneth cells secrete factors that influence lymphangiogenesis.

Main Methods:

• Used a mouse model with inducible Paneth cell depletion and partial portal vein ligation to induce portal hypertension.
• Performed mRNA sequencing, immunohistochemistry, and in vitro assays using organoids and lymphatic endothelial cells.
• Conducted secretome analysis to identify proteins secreted by Paneth cells.

Main Results:

• Absence of Paneth cells altered intestinal gene expression and decreased lymphangiogenic gene expression in portal hypertensive mice.
• Reduced proliferation of intestinal and mesenteric lymphatic vessels was observed in mice lacking Paneth cells.
• Paneth cell-conditioned media enhanced lymphatic endothelial cell tube formation and wound healing in vitro, with secretome analysis revealing proteins involved in lipid metabolism and cell growth.

Conclusions:

• Intestinal microbiota signals stimulate Paneth cells to secrete factors that modulate the intestinal and mesenteric lymphatic vessel network during experimental portal hypertension.
• Paneth cells play a significant role in regulating lymphangiogenesis in the context of portal hypertension.