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Publication : Absence of CCR6 inhibits CD4+ regulatory T-cell development and M-cell formation inside Peyer's patches.

First Author  Lügering A Year  2005
Journal  Am J Pathol Volume  166
Issue  6 Pages  1647-54
PubMed ID  15920150 Mgi Jnum  J:98816
Mgi Id  MGI:3579970 Doi  10.1016/S0002-9440(10)62475-3
Citation  Lugering A, et al. (2005) Absence of CCR6 Inhibits CD4+ Regulatory T-Cell Development and M-Cell Formation inside Peyer's Patches. Am J Pathol 166(6):1647-54
abstractText  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.
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