Autocrine regulation of T cell motility by calreticulin-thrombospondin-1 interaction.
The mechanisms regulating T lymphocyte migration within the extracellular matrix are not understood. We show in this study that the thrombospondin-1 binding site of calreticulin, spanning aa 19-32, is a major triggering factor for T cell motility and migration within a three-dimensional collagen type 1 matrix, and that exogenous motogenic factors such as chemokines can stimulate migration via a calreticulin-thrombospondin-1 pathway. Endogenous calreticulin binding to the N-terminal domain of endogenous thrombospondin-1 elicited a motogenic signal to the T cells through the C-terminal domain of thrombospondin-1 and its cell surface receptor integrin-associated protein (CD47). Our data further revealed that thrombospondin-1 was expressed on the cell surface with a high turnover, and that PI3K and the Janus family of tyrosine kinases were required for T cell motility mediated through calreticulin, thrombospondin-1, and CD47. These results unveil an autocrine mechanism of calreticulin-thrombospondin-1-CD47 interaction for the control of T cell motility and migration within three-dimensional extracellular matrix substrata.
Li
Shu Shun
SS
Division of Clinical Immunology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
Forslöw
Anna
A
Sundqvist
Karl-Gösta
KG
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology; D019898:Autocrine Communication / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology; D051928:CD47 Antigen; D037282:Calreticulin / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D024042:Collagen Type I; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D019700:Thrombospondin 1 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D015032:Zinc / Q000502:physiology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; C515255:CXCL12 protein, human; D037282:Calreticulin; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D024042:Collagen Type I; D010446:Peptide Fragments; D019700:Thrombospondin 1; D006493:Heparin; D015032:Zinc