Pglyrp1-Cre marks distinct epithelial and immune lineages across mucosal sites

Area of Science:

• Immunology
• Cell Biology
• Genetics

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 of M cells remains a challenge.

Purpose of the Study:

• To generate and characterize a Peptidoglycan Recognition Protein 1 (Pglyrp1)-Cre knock-in mouse model for conditional genetic access to M cells.
• To investigate the expression patterns 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.
• Crossbreeding with reporter (Rosa26-tdTomato) and ablation (Rosa26GFP-DTA, Rosa26DTA, Rosa26iDTR) mouse lines.
• Analysis of Pglyrp1 promoter activity and cell depletion in gut and nasal-associated lymphoid tissues (NALT).

Main Results:

• Pglyrp1 promoter activity was strong in gut epithelial cells (including M cells) but heterogeneous in NALT, favoring immune cells.
• Cre-mediated ablation using Rosa26GFP-DTA resulted in perinatal lethality, indicating essential roles for Pglyrp1+ cells early in life.
• Rosa26DTA and Rosa26iDTR models showed minimal depletion of mucosal populations, including M cells, even at high toxin doses.

Conclusions:

• Pglyrp1 promoter activity differs significantly across mucosal tissues.
• Achieving M cell-specific targeting via Pglyrp1 is challenging due to promoter heterogeneity.
• The Pglyrp1-Cre mouse is a valuable tool for studying Pglyrp1-expressing lineages in mucosal immunity and homeostasis, despite not being M cell-restricted.