Intestinal M cells

Abstract

We have an enormous number of commensal bacteria in our intestine, moreover, the foods that we ingest and the water we drink is sometimes contaminated with pathogenic microorganisms. The intestinal epithelium is always exposed to such microbes, friend or foe, so to contain them our gut is equipped with specialized gut-associated lymphoid tissue (GALT), literally the largest peripheral lymphoid tissue in the body. GALT is the intestinal immune inductive site composed of lymphoid follicles such as Peyer's patches. M cells are a subset of intestinal epithelial cells (IECs) residing in the region of the epithelium covering GALT lymphoid follicles. Although the vast majority of IEC function to absorb nutrients from the intestine, M cells are highly specialized to take up intestinal microbial antigens and deliver them to GALT for efficient mucosal as well as systemic immune responses. I will discuss recent advances in our understanding of the molecular mechanisms of M-cell differentiation and functions.

Keywords: M cell; Spi-B; antigen uptake; enteroid; gut-associated lymphoid tissue (GALT).

Fig. 1

Schematic view of the intestinal mucosa. Mucus-producing goblet cells are scattered throughout the villus region (left), and the epithelium is covered by mucus. (Intraepithelial lymphocytes are not shown here.) DCs in lamina propria sometimes extend their dendrites through epithelium to probe luminal microbes, especially at the end of ileum. Anti-microbial peptide-secreting Paneth cells are found at the crypt base in the villous region. In the FAE covering the GALT lymphoid follicles (right), goblet cells are hardly seen, resulting in the loss of the mucus coat. Instead, 5–10% of FAE cells are M cells. The M-cell pocket is also depicted. Adapted from the webpage of the Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (http://leib.rcai.riken.jp/riken/index.html)

Fig. 2

Scanning electron micrograph of FAE and M cells. A, Scanning electron micrograph of the mucosal surface of an isolated murine Peyer’s patch. Five FAE regions (F) are surrounded by villi. B, A higher magnification of the FAE. Two M cells (M) are seen. The M-cell surface appears sunken compared with the surrounding enterocytes because of the absence of microvilli. Adapted from the webpage of the Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (http://leib.rcai.riken.jp/riken/index.html)

Fig. 3

Schematic view of GP2-mediated uptake of bacteria for mucosal immune responses. Adapted from the webpage of the Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (http://leib.rcai.riken.jp/riken/index.html)

Fig. 4

Schematic model of RANKL-induced M-cell differentiation. Upon RANKL stimulation of immature IECs, most likely transit-amplifying cells, the Spi-B transcription factor is induced to initiate M-cell differentiation. Some M-cell markers, such as Marcksl1 and Annexin V appear early after RANKL stimulation and their expression is RANKL-independent (64). By contrast, expression of the other M-cell markers after RANKL stimulation takes a longer time and is Spi-B-dependent (64). Among the markers examined, GP2 expression occurs last and is thought to be a marker of fully mature M cells. Adapted from the webpage of the Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (http://leib.rcai.riken.jp/riken/index.html)