Loss of ​beta2-integrin-mediated cytoskeletal linkage reprogrammes dendritic cells to a mature migratory phenotype

Morrison, Vicky Louise and James, Martyn John and Grzes, Katarzyna and Cook, Peter and Glass, David Gavin and Savinko, Terhi and Lek, Hwee San and Gawden-Bone, Christian and Watts, Colin and Millington, Owain Richard and MacDonald, Andrew Scott and Fagerholm, Susanna Carola (2014) Loss of ​beta2-integrin-mediated cytoskeletal linkage reprogrammes dendritic cells to a mature migratory phenotype. Nature Communications, 5. 5359. ISSN 2041-1723

[img]
Preview
 Text (Morrison-etal-NC-2014-Loss-of-beta2-integrin-mediated-cytoskeletal-linkage-reprograms)
Morrison_etal_NC_2014_Loss_of_beta2_integrin_mediated_cytoskeletal_linkage_reprograms.pdf
Accepted Author Manuscript
Download (8MB)| Preview

    Abstract

    The actin cytoskeleton has been reported to restrict signalling in resting immune cells. Beta2-integrins, which mediate adhesion and cytoskeletal organization, are emerging as negative regulators of myeloid cell-mediated immune responses, but the molecular mechanisms involved are poorly understood. Here, we show that loss of the interaction between beta2-integrins and kindlin-3 abolishes the actin-linkage of integrins and the GM-CSF receptor in dendritic cells. This leads to increased GM-CSF receptor/Syk signalling, and to the induction of a transcriptional programme characteristic of mature, migratory dendritic cells, accumulation of migratory dendritic cells in lymphoid organs, and increased Th1 immune responses in vivo. We observe increased GM-CSF responses and increased survival in neutrophils where the interaction between integrin and the cytoskeleton is disrupted. Thus, ligand-reinforced beta2-integrin tail interactions restrict cytokine receptor signalling, survival, maturation and migration in myeloid cells and thereby contribute to immune homeostasis in vivo.

    Creators(s): Morrison, Vicky Louise, James, Martyn John, Grzes, Katarzyna, Cook, Peter, Glass, David Gavin, Savinko, Terhi, Lek, Hwee San, Gawden-Bone, Christian, Watts, Colin, Millington, Owain Richard ORCID logoORCID: https://orcid.org/0000-0002-3026-6550, MacDonald, Andrew Scott and Fagerholm, Susanna Carola;
    Item type:Article
    ID code:52928
    Keywords:immunology, actin cytoskeleton, dendritic cells, Pharmacy and materia medica, Biochemistry, Genetics and Molecular Biology(all), Chemistry(all), Physics and Astronomy(all)
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Technology and Innovation Centre > Photonics
    Depositing user: Pure Administrator
    Date deposited:06 May 2015 13:44
    Last modified:07 Aug 2020 04:07
    URI:https://strathprints.strath.ac.uk/id/eprint/52928
    Export data:
    CORE (COnnecting REpositories)