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 (https://doi.org/10.1038/ncomms6359)
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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.
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Item type: Article ID code: 52928 Dates: DateEvent28 October 2014Published23 September 2014AcceptedSubjects: Medicine > Pharmacy and materia medica Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Technology and Innovation Centre > PhotonicsDepositing user: Pure Administrator Date deposited: 06 May 2015 13:44 Last modified: 23 Feb 2024 01:41 URI: https://strathprints.strath.ac.uk/id/eprint/52928