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(American Journal of Pathology. 2005;166:1647-1654.)
© 2005 American Society for Investigative Pathology

Absence of CCR6 Inhibits CD4⁺ Regulatory T-Cell Development and M-Cell Formation inside Peyer’s Patches

Andreas Lügering^*, Martin Floer^*, Sabine Westphal^*, Christian Maaser^*, Thomas W. Spahn^*, M. Alexander Schmidt, Wolfram Domschke^*, Ifor R. Williams and Torsten Kucharzik^*

From the Departments of Medicine B^* and Infectiology, University of Münster, Münster, Germany; and the Departments of Pathology and Laboratory Medicine and of Dermatology, Emory University School of Medicine, Atlanta, Georgia

The chemokine Mip3 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 Mip3 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 Mip3 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.

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