One of the most essential functions of a cell is the ability to rearrange the cytoskeleton in order to change shape, transport proteins, intercellular communications and to push the cell body forward to be able to migrate. Cell migration is a central process in all-living organisms from the early embryogenesis to the maintenance of essential functions like wound healing or a functional immune system and, it is therefore important to be able to control cell movement and adhesion. 80% of the mortality in cancer is caused by metastasis of daughter cells from mother tumors into new niches/organs. The mechanism behind this is not very well understood. One of the most important players involved in mobility of the cell and in cell-cell contacts like the immunology synapse is a group of adhesion molecules called integrins. Despite decades of studying these events, our knowledge on how these adhesion proteins are reorganized and reused is very limited, especially in fast moving cells like leukocytes and tumor cells.
Our research group is interested in how to understand how integrins are regulated and reused, since de-novo synthesis would not be economic to any given cell. We are in particular interested in the integrin called LFA-1, which is the major integrin used by T lymphocytes. We want to better understand how LFA-1 is intracellularly transported and reused in a migrating cell as well in the immunological synapse and how this is perturb in diseases like cancer and autoimmunity.
V Junghans, M Chouliara, A De Cunha Santos, L Svensson, J Petersen, J Rossjohn, S Davis and P Jönsson. Two-dimensional Dissociation Constant of TCR binding peptide MHC and the Influence of Cellular Context. Frontiers in Immunology in press 2020
H Persson, W Potrzebowska, K Potrzebowska and L Svensson. Spatial mapping of affinity changes of the integrin LFA-1 during cell migration using clusters identified based on local density. Journal of Biophotonics, in press
K Potrzebowska, J Lehtonen, M Samuelsson, L Svensson. Flow Cytometry Assay for Recycling of LFA-1 in T-lymphocytes. Journal of Bio-protocol, in press
J Lehtonen, K Potrzebowska, M Samuelsson, L Svensson. Integrin Dependent RhoB Activation Assay Using Leukocytes. Journal of Bio-protocol, in press
M Samuelsson, K Potrzebowska, J Lehtonen, J Beech, K Skorova, H Uronen-Hansson, L Svensson. RhoB controls Rab11-mediated recycling and surface reappearance of LFA-1 in migrating T lymphocytes. Science Signaling 2017 Dec12:10(509)
J Rak, K Potrzebowska, K Foster, K Komorowska, M Safaee Talkhoncheh, T Torngren, A Kvist, L Svensson, D Bonnet, J Larsson. Cytohesin 1 regulates homing and engraftment of human hematopoietic stem and progenitor cells. Blood, 2017 129:950-958;
M Kadivar, J Petersson, L Svensson*,** and J Marsal*,**. TCRγδ+ CD8αβ+: a third functionally active subsets of γδ-T cells enriched within the gut. *Shared senior authorships, **Corresponding authors. Journal of Immunology 2016 Dec 15; 197 (12)
G Burn, G Cornish, K Potrzebowska, M Samuelsson, J Griffie, N Pernodet,G Ashdown, M Yates, S Minoughan, S Sachs, C Sanchez-Blanco, H Purvis, F Clarke, R Brownlie, T Vyse, D Rawlings, R Zamoyska, D Owen*, L. Svensson*,** and Andrew P. Cope*,**. Superresolution imaging of the cytoplasmic phosphatase PTPN22 links integrin-mediated T cell adhesion with autoimmunity. *Shared senior authorships, **Corresponding authors. Science Signaling, 2016 Oct 4;9(448):ra99.
N Arteaga-Marrero, C Rygh, J Mainou-Gomez, K Nylund, D Roehrich, J Heggdal, P Matulaniec, O Gilja, R Reed, L Svensson, N Lutay, and D Olsen. Multimodal approach to assess tumour vasculature and potential treatment effect with DCE-US and DCE-MRI quantification in CWR22 prostate tumour xenografts. Contrast Media Mol Imaging. 2015 Nov-Dec;10(6):428-37. doi: 10.1002/cmmi.1645. Epub 2015 May 26.
B Simpson, K Yarbrough, N Hogg, L Svensson, A McDowall, W Daley, O. Abdul-Rahman. A new leukocyte hyperadhesion syndrome of delayed cord separation, skin infection, and nephrosis. Pediatrics 2014 Jan;133(1):e257-62
N Bartolini, M Thelin, L Svensson, A Malmström, M Maccarana. Iduronic acid in chondroitin/dermatan sulfate affects migration of aortic smooth muscle cells. PloSONE 2013 Jul 2;8(7):e66704
K Svensson, H Christianson, A Wittrup, E Bourseau-Guilmain, E Lindqvist, L Svensson, M Mörgelin, M Belting. Exosome uptake depends on ERK1/2-heat shock protein 27 signalling and lipid raft-mediated endocytosis negatively regulated by caveolin-1. J Biol Chem May 7 2013
A Ramsay, R Evans, S Kiaii, L Svensson, N Hogg, and J Gribben. Chronic lymphocytic leukemia cells induce defective LFA-1-directed T cell motility by altering Rho GTPase signaling that is reversible with lenalidomide. Blood 2013 April 4;121(14):2704-14
R Brownlie, L Miosge, D Vassilakos, L Svensson, A Cope and R Zamoyska. Lack of the Phosphatase PTPN22 Increases Adhesion of Murine Regulatory T Cells to Improve their Immunosuppressive. Sci Signal. 2012;5 (252):ra87 23193160
L Svensson, P Stanley, F Willenbrock and N Hogg. The Gαq/11 proteins contribute to LFA-1-mediated migration of T cells by promoting integrin turnover. PloSONE 2012;7(6):e38517. doi: 10.1371/journal.pone.0038517. Epub 2012 Jun 11
R Evans, A Lellouch, L Svensson, A McDowall and N Hogg. The integrin LFA-1 signals through ZAP-70 to control the migration of T lymphocytes. Blood. 2011 Mar 24;117 (12):3331-42. Epub 2011 Jan
L Svensson*, A McDowall, K Giles, P Stanley, S Feske and N Hogg. Calpain 2 controls the turnover of LFA-1 adhesions on migrating T lymphocytes. PloSONE 2010 Nov 5:11e15090
A McDowall*, L Svensson*, I Patzak, P Stanley, K Howarth, H Sabnis, M Briones and N Hogg. The kindlin-3 gene in a new Leukocyte Adhesion Deficiency-III patient has two mutations with distinctive effects on leukocyte function. Blood. 2010 Jun 10;115 (23):4834-42 *These authors contributed equally to this study
H. Sabnis, A. Kirpalani, J. Horan, A. McDowall, L. Svensson, S. Jobe, T. Merck, N. Hogg and M. Briones. Leukocyte Adhesion Deficiency–III: A novel case in an African-American patient. Pediatr Blood Cancer. 2010 Jul 15;55 (1):180-2
L Svensson*, K Howarth*, A McDowall, I Patzak, R Evans, S Ussar, M Moser, A Metin, M Fried, I Tomlinson and N Hogg. Leukocyte Adhesion Deficiency-III (LAD-III) is caused by mutations in the adhesion protein Kindlin-3. Nature Medicine 2009; 15: 306-312. *These authors contributed equally to this study