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.