@article{bf60e2f6c0c3410d9c3f2f70ae01d436,
title = "Normality sensing licenses local T cells for innate-like tissue surveillance",
abstract = "The increasing implication of lymphocytes in general physiology and immune surveillance outside of infection poses the question of how their antigen receptors might be involved. Here, we show that macromolecular aggregates of intraepidermal γδ T cell antigen receptors (TCRs) in the mouse skin aligned with and depended on Skint1, a butyrophilin-like (BTNL) protein expressed by differentiated keratinocytes (KCs) at steady state. Interruption of TCR-mediated {\textquoteleft}normality sensing{\textquoteright} had no impact on γδ T cell numbers but altered their signature phenotype, while the epidermal barrier function was compromised. In addition to the regulation of steady-state physiology, normality sensing licensed intraepidermal T cells to respond rapidly to subsequent tissue perturbation by using innate tumor necrosis factor (TNF) superfamily receptors. Thus, interfering with Skint1-dependent interactions between local γδ T cells and KCs at steady state increased the susceptibility to ultraviolet B radiation (UVR)-induced DNA damage and inflammation, two cancer-disposing factors.",
author = "McKenzie, {Duncan R.} and Rosie Hart and Nourdine Bah and Ushakov, {Dmitry S.} and Miguel Mu{\~n}oz-Ruiz and Regina Feederle and Hayday, {Adrian C.}",
note = "Funding Information: We thank J. Strid (Imperial College London) and T. Zal (UT Southwestern) for advice; M. Battilocci and F. Watt (KCL) for advice and equipment and D. Calado (Francis Crick Institute) and T. Nitta, T. Narita and H. Takayanagi (University of Tokyo) for mice. We thank present and past members of our laboratory and the laboratory of D. Gibbons for discussions and advice, in particular O. Sobolev, A. Jandke, L. Monin, D. Moreno-Vicencio, V. Sofra, F. Cano and N. Roberts. We thank staff from the following Francis Crick Institute science technology platforms: biological research facility, flow cytometry, experimental histopathology, light microscopy, advanced sequencing, genomics equipment park (particularly O. O{\textquoteright}Neill) and cell services and staff at the Nikon Imaging Centre at KCL Guy{\textquoteright}s Hospital campus. This work was supported by The Francis Crick Institute, which receives core funding from Cancer Research UK (FC001093), the MRC (FC001093) and the Wellcome Trust (FC001093) (A.C.H.); by the Cancer Research UK, King{\textquoteright}s and City of London Cancer Centre; by the Wellcome Trust (106292/Z/14/Z and 100156/Z/12/Z; A.C.H.); by a Cancer Research Institute Irvington fellowship to D.R.M. and by a Cancer Research UK postdoctoral fellowship to R.H. Funding Information: We thank J. Strid (Imperial College London) and T. Zal (UT Southwestern) for advice; M. Battilocci and F. Watt (KCL) for advice and equipment and D. Calado (Francis Crick Institute) and T. Nitta, T. Narita and H. Takayanagi (University of Tokyo) for mice. We thank present and past members of our laboratory and the laboratory of D. Gibbons for discussions and advice, in particular O. Sobolev, A. Jandke, L. Monin, D. Moreno-Vicencio, V. Sofra, F. Cano and N. Roberts. We thank staff from the following Francis Crick Institute science technology platforms: biological research facility, flow cytometry, experimental histopathology, light microscopy, advanced sequencing, genomics equipment park (particularly O. O?Neill) and cell services and staff at the Nikon Imaging Centre at KCL Guy?s Hospital campus. This work was supported by The Francis Crick Institute, which receives core funding from Cancer Research UK (FC001093), the MRC (FC001093) and the Wellcome Trust (FC001093) (A.C.H.); by the Cancer Research UK, King?s and City of London Cancer Centre; by the Wellcome Trust (106292/Z/14/Z and 100156/Z/12/Z; A.C.H.); by a Cancer Research Institute Irvington fellowship to D.R.M. and by a Cancer Research UK postdoctoral fellowship to R.H. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = mar,
doi = "10.1038/s41590-021-01124-8",
language = "English",
volume = "23",
pages = "411--422",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "3",
}
