Details

Autor(en) / Beteiligte

• Weiß, Mariella
• Hernandez, Lola C
• Gil Montoya, Diana C
• Löhndorf, Anke
• Krüger, Aileen
• Kopdag, Miriam
• Uebler, Liana
• Landwehr, Marie
• Nawrocki, Mikolaj
• Huber, Samuel
• Woelk, Lena-Marie
• Werner, René
• Failla, Antonio V
• Flügel, Alexander
• Dupont, Geneviève
• Guse, Andreas H
• Diercks, Björn-Philipp

Titel

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

Ist Teil von

• Science signaling, 2023-06, Vol.16 (790), p.eabn9405

Ort / Verlag

United States

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 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 microdomains in a manner dependent on the kinase FAK, phospholipase C (PLC), and all three inositol 1,4,5-trisphosphate receptor (IP R) subtypes and promoted the nuclear translocation of the transcription factor NFAT-1. Mathematical modeling predicted that the formation of adhesion-dependent Ca microdomains required the concerted activity of two to six IP Rs and ORAI1 channels to achieve the increase in the Ca concentration in the ER-plasma membrane junction that was observed experimentally and that required SOCE. Further, adhesion-dependent Ca microdomains were important for the magnitude of the TCR-induced activation of T cells on collagen IV as assessed by the global Ca 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 microdomains, and blocking this low-level sensitization decreases T cell activation upon TCR engagement.