Maf is a regulator of differentiation for gut immune epithelial cell Microfold cell (M cell)

Abstract Background: Microfold cells (M cells) are a specialized subset of epithelial intestinal cells responsible for immunosurveillance of the gastrointestinal tract. M cells are located in the Peyer’s patches and are crucial for monitoring and the transcytosis of antigens, microorganisms, and pathogens via their mature receptor GP2. A mature M cell with Gp2 receptor aids in the uptake of antigens, which are passed through the single layer of epithelium and presented to underlying antigen-presenting cells and processed further downstream with B cells, T cells, and dendritic cells. Recent studies revealed several transcription factors and ligands responsible for the development and differentiation of mature M cells however, an exhaustive list of factors remains to be elucidated.Results: Our recent work on epigenetic regulation of M cells found Musculoaponeurotic fibrosarcoma transcription factor (Maf) to be regulated by PRC2 complex in M cell development. Using organoids grown in RANKL stimulating conditions, β-galactosidase staining of Peyer’s patch and Maf mouse knockout models, we demonstrate Maf’s role in M cell developments. We observed that Maf expression is specific to M cells in the Peyer’s patch and organoids grown in RANKL conditions gives rise to mature markers Gp2 expression as well as Maf expression. Organoids isolated from Maf knockout mice grown in RANKL conditions failed to differentiate into M cells and showed a severe lack of expression in M cell markers Conclusions: In this paper, we explore Maf’s critical role in M cell differentiation and maturation. Maf falls under the purview of RANKL signaling, is localized in the Peyer’s patches of the intestine, and is expressed by M cells. Given that, complete knockout of the Maf gene leads to a lethal phenotype, organoids isolated from Maf knockout mice and treated with RANKL exhibited impaired M cell development and a significant decrease in Gp2 expression. These findings reveal that Maf is an important regulator for M cell development and differentiation