VGLL4 modulates Paneth cells and sustains intestinal homeostasis

Area of Science:

• Gastroenterology
• Cell Biology
• Immunology

Background:

• Paneth cells are vital for small intestinal stem cell niche maintenance and immune homeostasis.
• They secrete niche factors and antimicrobial peptides (AMPs).
• The role of VGLL4 in intestinal homeostasis and Paneth cell regulation is unexplored.

Purpose of the Study:

• To investigate the role of Vestigial-like family member 4 (VGLL4) in maintaining small intestinal homeostasis.
• To elucidate VGLL4's regulatory function in Paneth cells.

Main Methods:

• Analysis of VGLL4 expression in response to irradiation and DSS-induced colitis.
• Assessment of Paneth cell numbers and AMPs production in VGLL4-deficient models.
• Investigation of VGLL4's molecular interactions with TEAD4, ATOH1, and TCF4.
• Examination of gut microbiota composition.

Main Results:

• VGLL4 expression is downregulated in intestinal injury models and human colitis.
• Loss of VGLL4 reduces Paneth cell numbers, decreases AMPs production, and causes gut dysbiosis.
• VGLL4 interacts with TEAD4/ATOH1 to promote Paneth cell differentiation via GFI1.
• VGLL4 interacts with TEAD4/TCF4 to induce defensin expression, maintaining microbiota.

Conclusions:

• VGLL4 plays a pivotal role in maintaining small intestinal homeostasis.
• VGLL4 regulates Paneth cell differentiation and function.
• VGLL4 is essential for maintaining gut microbiota composition and regenerative capacity.