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

• Published in: The American journal of pathology Vol. 166; no. 6; pp. 1647 - 1654
• Main Authors: Lügering, Andreas, Floer, Martin, Westphal, Sabine, Maaser, Christian, Spahn, Thomas W., Schmidt, M. Alexander, Domschke, Wolfram, Williams, Ifor R., Kucharzik, Torsten
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.06.2005; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Biological and medical sciences; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; Cell Movement - immunology; Cytokines - biosynthesis; Cytokines - immunology; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Flow Cytometry; Green Fluorescent Proteins; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Mice; Mice, Knockout; Microscopy, Electron, Transmission; Original Research Paper; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Peyer's Patches - cytology; Peyer's Patches - immunology; Peyer's Patches - ultrastructure; Receptors, CCR6; Receptors, Chemokine - deficiency; Receptors, Chemokine - immunology; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; Cell proliferation; Anatomic pathology; Peyer patch; CCR6 chemokine receptor; T-Lymphocyte; Inhibitor; Chemokine receptor; CC chemokine; Regulatory cell
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)62475-3

The chemokine Mip3α 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 Mip3α 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 Mip3α 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.