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McKenzie, D.R.* ; Hart, R.* ; Bah, N.* ; Ushakov, D.S.* ; Muñoz-Ruiz, M.* ; Feederle, R. ; Hayday, A.C.*

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

Nat. Immunol. 23, 411–422 (2022)
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Open Access Gold (Paid Option)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Lymphoid Stress-surveillance; Gamma-delta Tcr; Up-regulation; Genome-wide; Receptor; Skint-1; Growth; Keratinocytes; Amphiregulin; Maintenance
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Quellenangaben Volume: 23, Issue: , Pages: 411–422 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Monoclonal Antibody (IDO-MAB)
Grants Wellcome Trust