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

Peter Di Marco Barros (1, 2, 3) , Natalie Roberts (1) , Peter Dart (1, 2, 4) , Peter Vantourout (2) , Anett Jandke (1) , Peter Nussbaumer (2) , Livija Deban (1) , Sara Cipolat (1) , Rosie Hart (1) , Maria Luisa Iannitto (2) , Adam Laing (2) , Bradley Spencer-Dene (1) , Philip East (1) , Deena Gibbons (2) , Peter Irving (4) , Pablo Pereira (5) , Ulrich Steinhoff (6) , Adrian Hayday (1, 2)

1 The Francis Crick Institute [London]
2 King‘s College London
3 UCL - University College of London [London]
4 Guy's and St Thomas' Hospital [London]
5 Département d'Immunologie - Department of Immunology
6 Philipps Universität Marburg = Philipps University of Marburg

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.

Domaines: Immunologie

Peter Di Marco Barros, Natalie Roberts, Peter Dart, Peter Vantourout, Anett Jandke, et al.. Epithelia Use Butyrophilin-like Molecules to Shape Organ-Specific γδ T Cell Compartments. Cell, 2016, 167 (1), pp.203-218.e17. ⟨10.1016/j.cell.2016.08.030⟩. ⟨pasteur-02166692⟩