Location matters for immunosuppression In the gut, food antigens and resident microbes can trigger unwanted immune responses. Immunosuppressive cell types in the gut, such as regulatory T cells (T _regs ) and intraepithelial T lymphocytes (IELs), help to keep these responses at bay. Sujino et al. report that the specific anatomical location within the gut shapes the properties of the suppressive T cell populations that reside there (see the Perspective by Colonna and Cervantes-Barragan). Using mice, they find that T _regs primarily reside in the lamina propria. T _regs migrate to the intestinal epithelium, where they convert to IELs in a process that depends on the microbiota and the loss of a specific transcription factor. T _regs and IELs also play distinct but complementary roles in suppressing intestinal inflammation. Science , this issue p. 1581 ; see also p. 1515