Exocrine gland-resident memory CD8 + T cells use mechanosensing for tissue surveillance.

Autor: Ruef N; Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland., Martínez Magdaleno J; Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland., Ficht X; Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 22, 4058 Basel, Switzerland., Purvanov V; Biotechnology Institute Thurgau (BITg) at the University of Konstanz, 8280 Kreuzlingen, Switzerland., Palayret M; Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland., Wissmann S; Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland., Pfenninger P; Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland., Stolp B; Department for Infectious Diseases, Integrative Virology, Center for Integrative Infectious Disease Research, University Hospital Heidelberg, 69120 Heidelberg, Germany., Thelen F; Department of Medical Oncology and Hematology, University of Zürich and University Hospital Zürich, 8091 Zürich, Switzerland., Barreto de Albuquerque J; Division of Experimental Pathology, Institute of Pathology, University of Bern, 3008 Bern, Switzerland., Germann P; Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain., Sharpe J; Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain.; European Molecular Biology Laboratory (EMBL) Barcelona, 08003 Barcelona, Spain.; Institucio' Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Spain., Abe J; Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland., Legler DF; Biotechnology Institute Thurgau (BITg) at the University of Konstanz, 8280 Kreuzlingen, Switzerland.; Faculty of Biology, University of Konstanz, 78464 Konstanz, Germany.; Theodor Kocher Institute, University of Bern, 3011 Bern, Switzerland., Stein JV; Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2023 Dec 22; Vol. 8 (90), pp. eadd5724. Date of Electronic Publication: 2023 Dec 22.
DOI: 10.1126/sciimmunol.add5724
Abstrakt: Tissue-resident CD8 + T cells (T RM ) continuously scan peptide-MHC (pMHC) complexes in their organ of residence to intercept microbial invaders. Recent data showed that T RM lodged in exocrine glands scan tissue in the absence of any chemoattractant or adhesion receptor signaling, thus bypassing the requirement for canonical migration-promoting factors. The signals eliciting this noncanonical motility and its relevance for organ surveillance have remained unknown. Using mouse models of viral infections, we report that exocrine gland T RM autonomously generated front-to-back F-actin flow for locomotion, accompanied by high cortical actomyosin contractility, and leading-edge bleb formation. The distinctive mode of exocrine gland T RM locomotion was triggered by sensing physical confinement and was closely correlated with nuclear deformation, which acts as a mechanosensor via an arachidonic acid and Ca 2+ signaling pathway. By contrast, naïve CD8 + T cells or T RM surveilling microbe-exposed epithelial barriers did not show mechanosensing capacity. Inhibition of nuclear mechanosensing disrupted exocrine gland T RM scanning and impaired their ability to intercept target cells. These findings indicate that confinement is sufficient to elicit autonomous T cell surveillance in glands with restricted chemokine expression and constitutes a scanning strategy that complements chemosensing-dependent migration.
Databáze: MEDLINE
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