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Updated: Jul 12, 2025
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Loss of NOD2 in macrophages improves colitis and tumorigenesis in a lysozyme-dependent manner
Camille Chauvin1,2, Katarina Radulovic3, Olivier Boulard4
1Univ. Lille, Institut National de la Santé Et de la Recherche Médicale (Inserm), Centre de Recherche Hospitalier Universitaire (CHU) Lille, Institut Pasteur de Lille, U1019, Lille, France.
Background:
Crohn's disease (CD) is a complex and poorly understood myeloid-mediated disorder. Genetic variants with loss of function in the NOD2 gene confer an increased susceptibility to ileal CD. While Nod2 in myeloid cells may confer protection against T-cell mediated ileopathy, it remains unclear whether it may promote resolution of the inflamed colon. In this study, we evaluated the function of Nod2 in myeloid cells in a model of acute colitis and colitis-associated colon cancer (CAC).
Methods:
To ablate Nod2 specifically within the myeloid compartment, we generated LysM mice. The role of NOD2 was studied in a setting of Dextran Sodium Sulfate (DSS)-induced colitis and in azoxymethane (AOM)/DSS model. Clinical parameters were quantified by colonoscopy, histological, flow cytometry, and qRT-PCR analysis.
Results:
Upon DSS colitis model, LysM mice lost less weight than control littermates and had less severe damage to the colonic epithelium. In the AOM/DSS model, endoscopic monitoring of tumor progression revealed a lowered number of adenomas within the colon of LysM mice, associated with less expression of Tgfb. Mechanistically, lysozyme M was required for the improved disease severity in mice with a defect of NOD2 in myeloid cells.
Conclusion:
Our results indicate that loss of Nod2 signaling in myeloid cells aids in the tissue repair of the inflamed large intestine through lysozyme secretion by myeloid cells. These results may pave the way to design new therapeutics to limit the inflammatory and tumorigenic functions of NOD2.
Insights
Loss of NOD2 signaling in myeloid cells promotes colon tissue repair and reduces inflammation and tumor growth. This suggests lysozyme secretion by myeloid cells is key for healing in inflammatory bowel disease.
Area of Science:
- Immunology
- Gastroenterology
- Oncology
Background:
- Crohn's disease (CD) is a myeloid-mediated disorder where NOD2 gene variants increase susceptibility.
- The role of myeloid cell NOD2 in colon inflammation and cancer resolution is unclear.
- This study investigates NOD2 function in myeloid cells during acute colitis and colitis-associated cancer (CAC).
Purpose of the Study:
- To evaluate the function of NOD2 in myeloid cells in models of acute colitis and CAC.
- To understand how NOD2 deficiency in myeloid cells impacts inflammatory and tumorigenic processes in the colon.
Main Methods:
- Generated LysM-cre mice to specifically ablate NOD2 in myeloid cells.
- Utilized Dextran Sodium Sulfate (DSS)-induced colitis and azoxymethane/DSS (AOM/DSS) models.
- Assessed clinical parameters via colonoscopy, histology, flow cytometry, and qRT-PCR.
Main Results:
- LysM-cre mice exhibited reduced weight loss and colonic epithelial damage in DSS colitis.
- AOM/DSS model showed fewer adenomas in LysM-cre mice, with decreased TGF-beta expression.
- Lysozyme M was identified as crucial for improved disease severity in NOD2-deficient myeloid cells.
Conclusions:
- Loss of NOD2 signaling in myeloid cells promotes colon tissue repair via lysozyme secretion.
- These findings suggest a therapeutic strategy targeting NOD2 to limit inflammation and tumorigenesis in the gut.
