The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells

Area of Science:

• Immunology
• Molecular Biology
• Gastroenterology

Background:

• RNA helicases are vital for cellular processes and implicated in viral immunity.
• In vivo data on tissue-specific RNA helicase function, especially in antibacterial responses, is limited.
• The role of Dhx15 in intestinal immunity and inflammation remains largely unexplored.

Purpose of the Study:

• To investigate the in vivo function of Dhx15 in intestinal antibacterial responses.
• To determine Dhx15's role in Paneth cell function and its impact on gut microbiota.
• To explore the association between Dhx15 and human inflammatory bowel disease.

Main Methods:

• Generation of intestinal epithelial cell (IEC)-specific Dhx15-deficient mice (Dhx15^ΔIEC).
• Generation of Paneth cell-specific Dhx15-deficient mice (Dhx15^ΔPaneth).
• Infection models using *Citrobacter rodentium* and dextran sodium sulfate (DSS)-induced colitis.
• Analysis of α-defensin production and intestinal microbiota composition.

Main Results:

• Dhx15^ΔIEC mice exhibited susceptibility to *Citrobacter rodentium* infection due to impaired α-defensin production.
• Dhx15^ΔPaneth mice showed increased susceptibility to DSS-induced colitis and gut dysbiosis.
• Reduced Dhx15 protein levels were observed in human ulcerative colitis (UC) patients.

Conclusions:

• Dhx15 is a key regulator of Wnt-induced α-defensins in Paneth cells.
• Dhx15 plays a critical role in the intestinal antimicrobial response and maintaining gut homeostasis.
• Dhx15 deficiency contributes to intestinal inflammation and may be implicated in ulcerative colitis pathogenesis.