Epithelia Use Butyrophilin-like Molecules to Shape Organ-Specific γδ T Cell Compartments

作者：Rafael Di Marco Barros, Natalie Roberts, Robin Dart, Pierre Vantourout, Anett Jandke, Oliver Nussbaumer, Livija Deban, Sara Cipolat, Rosie Hart, Maria Luisa Iannitto, Adam Laing, Bradley Spencer‐Dene, Philip East, Deena L. Gibbons, Peter M. Irving, Pablo Pereira, Ulrich Steinhoff, Adrian Hayday · 发表于：Cell · 年份：2016 · DOI：10.1016/j.cell.2016.08.030 · 被引用次数：370 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Immunotherapy and Immune Responses

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.