Pglyrp1-Cre Marks Distinct Epithelial and Immune Lineages Across Mucosal Sites

Area of Science:

• Immunology
• Gastroenterology
• Microbiology

Background:

• Mucosa-associated lymphoid tissue (MALT) is crucial for initiating immune responses at mucosal surfaces.
• Microfold (M) cells within MALT sample antigens and present them to immune cells.
• Selective *in vivo* manipulation tools for M cells are limited.

Purpose of the Study:

• To generate and characterize a Pglyrp1-Cre knock-in mouse model for conditional genetic access to M cells.
• To investigate the promoter activity of Pglyrp1 in different mucosal tissues.
• To assess the feasibility of targeting Pglyrp1-expressing cells for functional studies.

Main Methods:

• Generation of a Pglyrp1-Cre knock-in mouse.
• Utilized Rosa26-tdTomato reporter mice to assess promoter activity.
• Performed Cre-mediated ablation using DTA-based models (Rosa26^GFP-DTA, Rosa26^DTA, Rosa26^iDTR).

Main Results:

• Strong Pglyrp1 promoter activity was observed in gut epithelial cells, including goblet and M cells.
• Nasal-associated lymphoid tissue (NALT) showed heterogeneous activity, skewed towards immune cells like neutrophils.
• Cre-mediated ablation using Rosa26^GFP-DTA resulted in perinatal lethality, indicating early life roles for Pglyrp1+ cells.
• Rosa26^DTA and Rosa26^iDTR models showed minimal depletion of mucosal populations, including M cells.

Conclusions:

• The Pglyrp1-Cre mouse exhibits tissue-specific promoter activity, demonstrating potential for studying Pglyrp1-expressing lineages.
• Achieving M cell-specific targeting remains challenging with current ablation models.
• The Pglyrp1-Cre mouse is a valuable tool for exploring Pglyrp1-expressing cell functions in mucosal immunity and homeostasis, despite not being M cell-restricted.