Transcription factor Spi-B–dependent and –independent pathways for the development of Peyer's patch M cells

Abstract

Although many of the biological features of microfold cells (M cells) have been known for many years, the molecular mechanisms of M-cell development and antigen recognition have remained unclear. Here, we report that Umod is a novel M-cell-specific gene, the translation products of which might contribute to the uptake function of M cells. Transcription factor Spi-B was also specifically expressed in M cells among non-hematopoietic lineages. Spi-B-deficient mice showed reduced expression of most, but not all, other M-cell-specific genes and M-cell surface markers. Whereas uptake of Salmonella Typhimurium via M cells was obviously reduced in Spi-B-deficient mice, the abundance of intratissue cohabiting bacteria was comparable between wild-type and Spi-B-deficient mice. These data indicate that there is a small M-cell population with developmental regulation that is Spi-B independent; however, Spi-B is probably a candidate master regulator of M-cell functional maturation and development by another pathway.

M Cells

“…Transcriptional profiling of gene expression by the isolated FAE and by sorted M cells using techniques such as microarrays has led to the identification of a series of genes selectively expressed by intestinal M cells that can be used as valuable additional markers for these cells (Lo et al, 2003;Hase et al, 2005;Verbrugghe et al, 2006;Terahara et al, 2008;Nakato et al, 2009;Sato et al, 2012). Some of the best-characterized members of this new generation of M cell markers are listed in Table 1.…”

RANKL regulates differentiation of microfold cells in mouse nasopharynx-associated lymphoid tissue (NALT)

“…The receptor activator of nuclear factor-!B (RANK) and its ligand (RANKL) are indispensable for initiating M-cell differentiation from Lgr5-positive epithelial stem cells (de Lau et al 2012;Knoop et al 2009). RelB and Spi-B, downstream transcription factors of RANKL-RANK signaling, were previously shown to be essential for the subsequent differentiation process toward the maturation of intestinal M cells (Kimura et al 2015;Sato et al 2013;de Lau et al 2012;Kanaya et al 2012). On the other hand, information regarding the factors required for M-cell differentiation in NALT is limited.…”

“…Spi-B is a transcription factor that is essential for M-cell differentiation (de Lau et al 2012;Kanaya et al 2012;Sato et al 2013). Immunohistochemistry for Spi-B labeled a number of nuclei in the FAE of NALT (Fig.…”

Visualization of the entire differentiation process of murine M cells: suppression of their maturation in cecal patches

“…4 In addition to GP2, several M-cell-specific molecules have been identified: Tnfaip2, 5 Pglyrp1, 6 Anxa5, 7 Ccl9, 8 Marksl1, 9 and Spi-B. [10][11][12] However, comparison of their distribution on the entire FAE has not been analyzed in detail due to limited methods.…”