Myeloid vitamin D receptor regulates Paneth cells and microbial homeostasis
Abstract
Cross talk between immune cells and the intestinal crypt is critical in maintaining intestinal homeostasis. Recent studies highlight the direct impact of vitamin D receptor (VDR) signaling on intestinal and microbial homeostasis. However, the tissue‐specific role of immune VDR signaling is not fully understood. Here, we generated a myeloid‐specific VDR knockout (VDRΔLyz) mouse model and used a macrophage/enteroids coculture system to examine tissue‐specific VDR signaling in intestinal homeostasis. VDRΔLyz mice exhibited small intestine elongation and impaired Paneth cell in maturation and localization. Coculture of enteroids with VDR−/− macrophages increased the delocalization of Paneth cells. VDRΔLyz mice exhibited significant changes in the microbiota taxonomic and functional files, and susceptibility to Salmonella infection. Interestingly, loss of myeloid VDR impaired Wnt secretion in macrophages, thus inhibiting crypt β‐catenin signaling and disrupting Paneth cell differentiation in the epithelium. Taken together, our data have demonstrated that myeloid cells regulate crypt differentiation and the microbiota in a VDR‐dependent mechanism. Dysregulation of myeloid VDR led to high risks of colitis‐associated diseases. Our study provided insight into the mechanism of immune/Paneth cell cross talk in regulating intestinal homeostasis.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 23, 2023
- Source ID
- 10.1096/fj.202202169rr
Entities
People
- Danika S. Bakke
- Destiny Ogbu
- Jilei Zhang
- Jun Sun
- Yinglin Xia
- Yongguo Zhang
Organizations
- Jesse Brown VA Medical Center
- National Institutes of Health
- United States Department of Defense
- University of Illinois Urbana–Champaign