Stem- and Paneth cell-specific CD74 functions control gut immune responses

What To Know

This NIH Reporter project describes funded preclinical research investigating CD74 (a receptor and MHCII-associated protein) in specific intestinal epithelial cell types — notably stem cells and Paneth cells — and how those functions affect mucosal immunity, epithelial regeneration, and responses to pathogen challenge.

The team will use conditional Cd74 knockout mice, cell-type specific models, and human enteroids to test roles in stem cell renewal, Paneth cell antigen presentation, and epithelial healing.

The work builds on observations that epithelial CD74/MHCII expression rises during infection or chronic inflammation, that epithelial or stem-cell Cd74 loss increases susceptibility to experimental colitis in mice, and that Paneth cells express high CD74/MHCII and may present bacterial antigen.

The aims focus on defining epithelial CD74 contributions to regeneration and the impact of Paneth cell CD74–MHCII on local immune modulation.

If successful, the project aims to identify cell-type specific immune or regenerative nodes that could be targeted to improve mucosal healing or host defense — findings that would inform later translational research rather than immediate clinical changes.