Morrison, V. L. et al. (2014) Loss of beta2-integrin-mediated cytoskeletal linkage reprogrammes dendritic cells to a mature migratory phenotype. Nature Communications, 5, 5359. (doi: 10.1038/ncomms6359) (PMID:25348463) (PMCID:PMC4258606)
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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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Morrison, Dr Vicky |
Authors: | Morrison, V. L., James, M. J., Grzes, K., Cook, P., Glass, D. G., Savinko, T., Lek, H. S., Gawden-Bone, C., Watts, C., Millington, O. R., MacDonald, A. S., and Fagerholm, S. C. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Nature Communications |
Publisher: | Nature Publishing Group |
ISSN: | 2041-1723 |
ISSN (Online): | 2041-1723 |
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