Adhesion to laminin-1 and collagen IV induces the formation of Ca 2+ microdomains that sensitize mouse T cells for activation.

Autor:	Weiß M; Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Hernandez LC; Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Gil Montoya DC; Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Löhndorf A; Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Krüger A; Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Kopdag M; Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Uebler L; Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Landwehr M; Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Nawrocki M; Section of Molecular Immunology und Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Huber S; Section of Molecular Immunology und Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Woelk LM; Department of Computational Neuroscience, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Werner R; Department of Computational Neuroscience, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Failla AV; Microscopy Imaging Facility (UMIF), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Flügel A; Institute for Neuroimmunology and Multiple Sclerosis Research, University Medical Centre Göttingen, 37075 Göttingen, Germany., Dupont G; Unité de Chronobiologie Théorique, Faculté des Sciences, CP231, Université Libre de Bruxelles (ULB), B-1050 Brussels, Belgium., Guse AH; Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Diercks BP; Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Jazyk:	angličtina
Zdroj:	Science signaling [Sci Signal] 2023 Jun 20; Vol. 16 (790), pp. eabn9405. Date of Electronic Publication: 2023 Jun 20.
DOI:	10.1126/scisignal.abn9405
Abstrakt:	During an immune response, T cells migrate from blood vessel walls into inflamed tissues by migrating across the endothelium and through extracellular matrix (ECM). Integrins facilitate T cell binding to endothelial cells and ECM proteins. Here, we report that Ca 2+ microdomains observed in the absence of T cell receptor (TCR)/CD3 stimulation are initial signaling events triggered by adhesion to ECM proteins that increase the sensitivity of primary murine T cells to activation. Adhesion to the ECM proteins collagen IV and laminin-1 increased the number of Ca 2+ microdomains in a manner dependent on the kinase FAK, phospholipase C (PLC), and all three inositol 1,4,5-trisphosphate receptor (IP 3 R) subtypes and promoted the nuclear translocation of the transcription factor NFAT-1. Mathematical modeling predicted that the formation of adhesion-dependent Ca 2+ microdomains required the concerted activity of two to six IP 3 Rs and ORAI1 channels to achieve the increase in the Ca 2+ concentration in the ER-plasma membrane junction that was observed experimentally and that required SOCE. Further, adhesion-dependent Ca 2+ microdomains were important for the magnitude of the TCR-induced activation of T cells on collagen IV as assessed by the global Ca 2+ response and NFAT-1 nuclear translocation. Thus, adhesion to collagen IV and laminin-1 sensitizes T cells through a mechanism involving the formation of Ca 2+ microdomains, and blocking this low-level sensitization decreases T cell activation upon TCR engagement.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu