Absence of CCR6 inhibits CD4+ regulatory T-cell development and M-cell formation inside Peyer's patches.
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.
Lügering
Andreas
A
Department of Medicine B, University of Münster, Albert-Schweitzer-Strasse 33, D-48129 Münster, Germany. lugerin@uni-muenster.de
Floer
Martin
M
Westphal
Sabine
S
Maaser
Christian
C
Spahn
Thomas W
TW
Schmidt
M Alexander
MA
Domschke
Wolfram
W
Williams
Ifor R
IR
Kucharzik
Torsten
T
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D010581:Peyer's Patches / Q000166:cytology* / Q000276:immunology / Q000648:ultrastructure; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology
C498126:CCR6 protein, mouse; D016207:Cytokines; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D049452:Green Fluorescent Proteins