Glia maturation factor gamma regulates the migration and adherence of human T lymphocytes

dc.contributor.authorLippert, Dustin ND
dc.contributor.authorWilkins, John A
dc.date.accessioned2012-09-19T15:10:31Z
dc.date.available2012-09-19T15:10:31Z
dc.date.issued2012-04-18
dc.date.updated2012-09-19T15:10:32Z
dc.description.abstractAbstractBackgroundLymphocyte migration and chemotaxis are essential for effective immune surveillance. A critical aspect of migration is cell polarization and the extension of pseudopodia in the direction of movement. However, our knowledge of the underlying molecular mechanisms responsible for these events is incomplete. Proteomic analysis of the isolated leading edges of CXCL12 stimulated human T cell lines was used to identify glia maturation factor gamma (GMFG) as a component of the pseudopodia. This protein is predominantly expressed in hematopoietic cells and it has been shown to regulate cytoskeletal branching. The present studies were undertaken to examine the role of GMFG in lymphocyte migration.ResultsMicroscopic analysis of migrating T-cells demonstrated that GMFG was distributed along the axis of movement with enrichment in the leading edge and behind the nucleus of these cells. Inhibition of GMFG expression in T cell lines and IL-2 dependent human peripheral blood T cells with shRNAmir reduced cellular basal and chemokine induced migration responses. The failure of the cells with reduced GMFG to migrate was associated with an apparent inability to detach from the substrates that they were moving on. It was also noted that these cells had an increased adherence to extracellular matrix proteins such as fibronectin. These changes in adherence were associated with altered patterns of β1 integrin expression and increased levels of activated integrins as detected with the activation specific antibody HUTS4. GMFG loss was also shown to increase the expression of the β2 integrin LFA-1 and to increase the adhesion of these cells to ICAM-1.ConclusionsThe present studies demonstrate that GMFG is a component of human T cell pseudopodia required for migration. The reduction in migration and increased adherence properties associated with inhibition of GMFG expression suggest that GMFG activity influences the regulation of integrin mediated adhesion.
dc.description.versionPeer Reviewed
dc.identifier.citationBMC Immunology. 2012 Apr 18;13(1):21
dc.identifier.doihttp://dx.doi.org/10.1186/1471-2172-13-21
dc.identifier.urihttp://hdl.handle.net/1993/8878
dc.language.rfc3066en
dc.rightsopen accessen_US
dc.rights.holderDustin ND Lippert et al.; licensee BioMed Central Ltd.
dc.titleGlia maturation factor gamma regulates the migration and adherence of human T lymphocytes
dc.typeJournal Article
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