Identifying human and murine M cells in vitro

Abstract

The study of M cells, a specialized epithelial cell type found in the follicle-associated epithelium, is hampered by the lack of a universal M cell marker. As such, many studies lack reliable and universally recognized methods to identify M cells in their proposed models. As a result of this it is difficult to ascertain whether the effects observed are due to the presence of M cells or an unaccounted variable. The outcome of this review is the thorough evaluation of the many M cell markers that have been used in the literature thus far and a proposed criterion for the identification of M cells for future publications. This will hopefully lead to an improvement in the quality of future publications in this field.

Keywords: Gp-2; M cells; UEA-1; enteroid; follicle-associated epithelium; organoid.

Figure 1.

The differentiation of M cells is triggered by ligation of the RANK receptor expressed by cells of the intestinal epithelium to its ligand, RANKL. This causes the activation of TRAF6-mediated NF-kB signaling and the induction of Ets transcription SpiB. M cells express different markers at during early and late stage development, with Gp2 being indicative of fully differentiated, mature M cells. Cytokines secreted by the follicle-associated epithelium, such as CCL20 and CCL9, have a chemotaxic effect toward CD11b+ dendritic cells that are present in the subepithelial dome. (A color version of this figure is available in the online journal.)

Figure 2.

M cells constitutively expressed by the follicle-associated epithelium express the mature M cell marker Gp2. They differentiate in response to RANKL stimulation and induction of SpiB. Alternatively, regular villous enterocytes can be prompted to differentiate into “villous” M cells that are only partially reminiscent of the M cell phenotype. Villous M cells are not restricted to the follicle-associated epithelium, express different markers and develop independently of SpiB. They are void of Gp2 expression and thus have an impaired transcytotic ability. (A color version of this figure is available in the online journal.)