The Ets Transcription Factor Spi-B Is Essential for the Differentiation of Intestinal Microfold (M) Cells

Intestinal microfold (M) cells are an enigmatic lineage of intestinal epithelial cells that initiate mucosal immune responses by uptake and transcytosis of luminal antigens. The mechanisms of M-cell differentiation are poorly understood as the rarity of these cells has hampered analysis. Exogenous RANKL administration can synchronously activate M-cell differentiation in mice. Here we show the Ets transcription factor Spi-B was induced early during M-cell differentiation. Absence of Spi-B silenced the expression of multiple M-cell markers and prevented the differentiation of M cells in mice. Oral antigen-specific T cell activation was significantly impaired in the intestine of Spib(−/−) mice. Our study demonstrates that intestinal M-cell lineage commitment requires Spi-B as a candidate master regulator.