10779/crick.12662708.v1 Rafael Di Marco Barros Rafael Di Marco Barros Natalie A Roberts Natalie A Roberts Robin J Dart Robin J Dart Pierre Vantourout Pierre Vantourout Anett Jandke Anett Jandke Oliver Nussbaumer Oliver Nussbaumer Livija Deban Livija Deban Sara Cipolat Sara Cipolat Rosie Hart Rosie Hart Maria Luisa Iannitto Maria Luisa Iannitto Adam Laing Adam Laing Bradley Spencer-Dene Bradley Spencer-Dene Philip East Philip East Deena Gibbons Deena Gibbons Peter M Irving Peter M Irving Pablo Pereira Pablo Pereira Ulrich Steinhoff Ulrich Steinhoff Adrian Hayday Adrian Hayday Epithelia use butyrophilin-like molecules to shape organ-specific γδ T cell compartments The Francis Crick Institute 2020 Animals Butyrophilins Gene Knockout Techniques Humans Intestinal Mucosa Mice Mice, Inbred C57BL Receptors, Antigen, T-Cell, gamma-delta T-Lymphocytes Thymus Gland Hayday FC001093 HP CB FC-ack BRF-ack 06 Biological Sciences 11 Medical and Health Sciences Developmental Biology 2020-07-17 16:35:02 Journal contribution https://crick.figshare.com/articles/journal_contribution/Epithelia_use_butyrophilin-like_molecules_to_shape_organ-specific_T_cell_compartments/12662708 Many body surfaces harbor organ-specific γδ T cell compartments that contribute to tissue integrity. Thus, murine dendritic epidermal T cells (DETCs) uniquely expressing T cell receptor (TCR)-Vγ5 chains protect from cutaneous carcinogens. The DETC repertoire is shaped by Skint1, a butyrophilin-like (Btnl) gene expressed specifically by thymic epithelial cells and suprabasal keratinocytes. However, the generality of this mechanism has remained opaque, since neither Skint1 nor DETCs are evolutionarily conserved. Here, Btnl1 expressed by murine enterocytes is shown to shape the local TCR-Vγ7(+) γδ compartment. Uninfluenced by microbial or food antigens, this activity evokes the developmental selection of TCRαβ(+) repertoires. Indeed, Btnl1 and Btnl6 jointly induce TCR-dependent responses specifically in intestinal Vγ7(+) cells. Likewise, human gut epithelial cells express BTNL3 and BTNL8 that jointly induce selective TCR-dependent responses of human colonic Vγ4(+) cells. Hence, a conserved mechanism emerges whereby epithelia use organ-specific BTNL/Btnl genes to shape local T cell compartments.