Normality sensing licenses local T cells for innate-like tissue surveillance

Duncan R. McKenzie, Rosie Hart, Nourdine Bah, Dmitry S. Ushakov, Miguel Muñoz-Ruiz, Regina Feederle, Adrian C. Hayday*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


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 ‘normality sensing’ 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.

Original languageEnglish
Pages (from-to)411-422
Number of pages12
JournalNature Immunology
Issue number3
Early online date14 Feb 2022
Publication statusPublished - Mar 2022

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