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Updated: Oct 30, 2025
Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine
Published on: May 21, 2012
Macrophages Compensate for Loss of Protein Tyrosine Phosphatase N2 in Dendritic Cells to Protect from Elevated
Larissa Hering1, Egle Katkeviciute1, Marlene Schwarzfischer1
1Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
Abstract:
Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) plays a critical role in the pathogenesis of inflammatory bowel diseases (IBD). Mice lacking PTPN2 in dendritic cells (DCs) develop skin and liver inflammation by the age of 22 weeks due to a generalized loss of tolerance leading to uncontrolled immune responses. The effect of DC-specific PTPN2 loss on intestinal health, however, is unknown. The aim of this study was to investigate the DC-specific role of PTPN2 in the intestine during colitis development. PTPN2fl/flxCD11cCre mice were subjected to acute and chronic DSS colitis as well as T cell transfer colitis. Lamina propria immune cell populations were analyzed using flow cytometry. DC-specific PTPN2 deletion promoted infiltration of B and T lymphocytes, macrophages, and DCs into the lamina propria of unchallenged mice and elevated Th1 abundance during acute DSS colitis, suggesting an important role for PTPN2 in DCs in maintaining intestinal immune cell homeostasis. Surprisingly, those immune cell alterations did not translate into increased colitis susceptibility in acute and chronic DSS-induced colitis or T cell transfer colitis models. However, macrophage depletion by clodronate caused enhanced colitis severity in mice with a DC-specific loss of PTPN2. Loss of PTPN2 in DCs affects the composition of lamina propria lymphocytes, resulting in increased infiltration of innate and adaptive immune cells. However, this did not result in an elevated colitis phenotype, likely because increased infiltration of macrophages in the intestine upon loss of PTPN2 loss in DCs can compensate for the inflammatory effect of PTPN2-deficient DCs.
Insights
Loss of Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) in dendritic cells (DCs) increases immune cell infiltration in the gut. However, this does not worsen colitis, as macrophages compensate for PTPN2-deficient DCs.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is implicated in inflammatory bowel diseases (IBD) pathogenesis.
- PTPN2 deficiency in dendritic cells (DCs) causes systemic inflammation and loss of immune tolerance.
- The role of DC-specific PTPN2 in intestinal immunity and colitis remains unexplored.
Purpose of the Study:
- To investigate the specific role of PTPN2 in dendritic cells (DCs) within the intestinal environment during colitis development.
- To determine if PTPN2 loss in DCs influences intestinal immune cell homeostasis and susceptibility to colitis.
Main Methods:
- Utilized PTPN2fl/flxCD11cCre mice models for acute and chronic DSS colitis and T cell transfer colitis.
- Analyzed lamina propria immune cell populations via flow cytometry.
- Investigated the impact of macrophage depletion using clodronate.
Main Results:
- DC-specific PTPN2 deletion led to increased infiltration of lymphocytes, macrophages, and DCs in the lamina propria of healthy mice.
- Elevated Th1 cell abundance was observed during acute DSS colitis.
- Surprisingly, DC-specific PTPN2 loss did not increase susceptibility to DSS or T cell transfer colitis.
- Macrophage depletion exacerbated colitis severity in mice lacking PTPN2 in DCs.
Conclusions:
- Loss of PTPN2 in DCs alters intestinal immune cell composition, increasing innate and adaptive immune cell infiltration.
- Despite immune cell alterations, DC-specific PTPN2 deficiency does not inherently increase colitis susceptibility.
- Increased macrophage infiltration in the intestine compensates for the inflammatory effects of PTPN2-deficient DCs, maintaining intestinal immune homeostasis.
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