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

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 aligne...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature immunology 2022-03, Vol.23 (3), p.411-422
Hauptverfasser: McKenzie, Duncan R., Hart, Rosie, Bah, Nourdine, Ushakov, Dmitry S., Muñoz-Ruiz, Miguel, Feederle, Regina, Hayday, Adrian C.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. Hayday and colleagues show that sustained Skint1-dependent interactions between murine intraepidermal γδ T cells and keratinocytes are required to maintain the homeostatic barrier function and phenotype of the intraepidermal γδ T cells, including their preparedness to respond appropriately to epidermal challenges.
ISSN:1529-2908
1529-2916
1529-2916
DOI:10.1038/s41590-021-01124-8