The gut epithelium constantly regenerates through the rapid proliferation and differentiation of intestinal stem cells (ISCs). In Cell, Biton et al. identify two subpopulations of proliferative Lgr5⁺ ISCs that express major histocompatibility class II (MHCII), process extracellular antigens and activate naive T cells. In intestinal organoid cultures, the addition of regulatory T cells or the anti-inflammatory cytokine IL-10 leads to the expansion of ISC populations; addition of the T_H1 subset of helper T cells or the cytokine IFN-γ induces the differentiation of ISCs into Paneth cells; and the addition of T_H2 cells or the cytokine IL-13 induces the differentiation of ISCs into tuft cells. In mice, infection with Salmonella enterica or Heligmosomoides polygyrus increases the frequency of MHCII⁺ ISCs and the number of Paneth cells or tuft cells, respectively. Mice that lack expression of MHCII on Lgr5⁺ ISCs or T cell–deficient

Nature Immunologyvolume 20, page1 (2019)