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Updated: Aug 17, 2026
Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
Absence of CCR6 inhibits CD4+ regulatory T-cell development and M-cell formation inside Peyer's patches
Andreas Lügering1, Martin Floer, Sabine Westphal
1Department of Medicine B, University of Münster, Albert-Schweitzer-Strasse 33, D-48129 Münster, Germany. lugerin@uni-muenster.de
Abstract:
The chemokine Mip3alpha is specifically expressed by the follicle-associated epithelia (FAE) covering intestinal Peyer's patches (PPs) and is the only known chemokine ligand for the chemokine receptor CCR6. Although CCR6-deficient mice are known to have a perturbed intestinal immune system, little is known about the specific impact of this interaction for Peyer's patch formation. To elucidate the effect of Mip3alpha on PP lymphocyte development, we used a CCR6/enhanced green fluorescent protein (EGFP) knock-in mouse model and analyzed lymphocyte development by immunohistochemistry and flow cytometry. PPs of CCR6-/- mice were significantly size-reduced with a proportional loss of B cells and T cells, whereas T-cell subsets were disturbed with a decreased CD4/CD8 ratio paralleled with a loss of regulatory CD4+ CD45Rb(low) T cells. The analysis of cytokine production by CCR6-expressing cells could demonstrate that CCR6 is involved in the regulation of cytokine secretion such as interleukin-12 by dendritic cells. Quantification of UEA-1+ cells inside the FAE showed reduced M-cell numbers in CCR6-deficient mice. These results suggest that the interaction of CCR6 with its ligand Mip3alpha is important for immune responses generated inside the PPs, particularly for the generation of regulatory CD4+ T cells residing inside PPs and for the formation of M cells.
Insights
The chemokine receptor CCR6 and its ligand Mip3alpha are crucial for Peyer
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- The chemokine Mip3alpha is specifically expressed by the follicle-associated epithelia (FAE) of intestinal Peyer's patches (PPs).
- Mip3alpha is the sole known chemokine ligand for the receptor CCR6.
- CCR6-deficient mice exhibit a perturbed intestinal immune system, but its specific role in Peyer's patch formation remains unclear.
Purpose of the Study:
- To investigate the impact of the Mip3alpha-CCR6 interaction on Peyer's patch (PP) lymphocyte development.
- To elucidate the role of CCR6 in the formation and function of Peyer's patches.
Main Methods:
- Utilized a CCR6/enhanced green fluorescent protein (EGFP) knock-in mouse model.
- Analyzed lymphocyte development using immunohistochemistry and flow cytometry.
- Assessed cytokine production by CCR6-expressing cells and quantified M-cell numbers.
Main Results:
- PPs in CCR6-/- mice were significantly smaller, with a proportional loss of B and T cells.
- T-cell subsets were disturbed, showing a decreased CD4/CD8 ratio and a loss of regulatory CD4+ CD45Rb(low) T cells.
- Reduced M-cell numbers were observed in FAE of CCR6-deficient mice, and CCR6 was implicated in regulating dendritic cell cytokine secretion (e.g., IL-12).
Conclusions:
- The CCR6-Mip3alpha interaction is vital for immune responses within Peyer's patches.
- This interaction is particularly important for the generation of regulatory CD4+ T cells in PPs.
- CCR6 signaling plays a key role in Peyer's patch formation, including M-cell development.
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