However, mature IEL express no CCR6. In the current study we show clearly

that the expression of CCR6 is related specifically to lin- c-kit+ cells inside CP, as cells outside CP lose CCR6 expression and are found positive for an alternate chemokine receptor not present on CP cells, CXCR3. Although lin- c-kit+ cells express various receptors as determined by PCR analysis, suggesting redundancy, CCR6 also seems to have a functional role, as data published by MacDonald et al.[18] suggest that CCR6 is important for the development of mature isolated lymphoid follicles (ILF) from CP. It can be speculated that CCR6 contributes to similar MAPK Inhibitor Library research buy events inside ILF and Peyer’s patches development as the latter are size-reduced significantly in the absence of a functional CCR6 receptor, while no change in micro-architecture can be found [19]. Most intriguingly, CCR6 seems to differentiate at least two different subsets of lin- c-kit+ cells that have not been find more appreciated in other studies, and the majority (>70%) of lin- c-kit+ cells are indeed found outside CP. Recently, Eberl et al. could show that basically all lin- c-kit+ cells express the orphan receptor RORγt. Immunohistochemical

studies have identified that these cells are located specifically within CP. The authors concluded that these cells are, rather, organizers of induced organized lymphoid tissue in adults (LTi cells) and do not participate in IEL development. However, our data show that the majority is of these cells is CCR6- (CXCR3+) and therefore found outside CP. It remains to be elucidated if both cell types are the progeny of a common precursor or if, functionally, they constitute different cellular lineages. In addition, it can be speculated that subsets of these cells might contribute to the IEL compartment in specialized settings. However, we were not able to find an influence of CCR6/Mip3α on Notch

signalling known to influence αβversusγδ lineage commitment. Strikingly, the flow cytometric phenotype of CCR6+ lin- c-kit+ cells correlates well with earlier data published by Kanamori et al., showing that CP cells are CD8- and partly positive for CD4, Cepharanthine while both types express similar levels of CD25, CD44 and CD127 [1]. Previous studies have attempted to identify CP-like structures in humans, but no clusters of c-kit positive cells could be identified. Initial trials by Moghaddami et al. found lymphoid structures with an epithelium resembling follicle-associated epithelium termed ‘lymphocyte-filled villi’[20]. These structures contain different leucocyte subsets such as major histocompatibility complex class II-positive dendritic cells, memory T cells and a variable amount of B cells. The authors concluded that the human gut does not contain CP. In contrast, ILF were appreciated in humans decades ago [21].