Autocrine regulation of T cell motility by calreticulin-thrombospondin-1 interaction
2005 (English)In: Journal of Immunology, ISSN 0022-1767, Vol. 174, no 2, 654-661 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2005. Vol. 174, no 2, 654-661 p.
IdentifiersURN: urn:nbn:se:umu:diva-4707PubMedID: 15634883OAI: oai:DiVA.org:umu-4707DiVA: diva2:143921