title: Annexin A6 regulates interleukin-2-mediated T-cell proliferation.
abstract: Annexin A6 (AnxA6) has been implicated in cell signalling by contributing to the organisation of the plasma membrane. Here we examined whether AnxA6 regulates signalling and proliferation in T cells. We used a contact hypersensitivity model to immune challenge wild-type (WT) and AnxA6(-/-) mice and found that the in vivo proliferation of CD4(+) T cells, but not CD8(+) T cells, was impaired in AnxA6(-/-) relative to WT mice. However, T-cell migration and signalling through the T-cell receptor ex vivo was similar between T cells isolated from AnxA6(-/-) and WT mice. In contrast, interleukin-2 (IL-2) signalling was reduced in AnxA6(-/-) compared with WT T cells. Further, AnxA6-deficient T cells had reduced membrane order and cholesterol levels. Taken together, our data suggest that AnxA6 regulates IL-2 homeostasis and sensitivity in T cells by sustaining a lipid raft-like membrane environment.
authors: EMBL Australia Node in Single Molecule Science, School of Medical Science, University of New South Wales (UNSW), Sydney, New South Wales, Australia.
authors: Rhea
authors: R
authors: Cornely
authors: EMBL Australia Node in Single Molecule Science, School of Medical Science, University of New South Wales (UNSW), Sydney, New South Wales, Australia.
authors: Abigail H
authors: AH
authors: Pollock
authors: Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
authors: Carles
authors: C
authors: Rentero
authors: School of Medicine, Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, Wollongong, Australia.
authors: Sarah E
authors: SE
authors: Norris
authors: Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
authors: Anna
authors: A
authors: Alvarez-Guaita
authors: Faculty of Pharmacy A15, University of Sydney, Sydney, New South Wales, Australia.
authors: Thomas
authors: T
authors: Grewal
authors: School of Medicine, Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, Wollongong, Australia.
authors: Todd
authors: T
authors: Mitchell
authors: Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.|Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors: Carlos
authors: C
authors: Enrich
authors: Department of Cell Biology, Institute of Ophthalmology, University College, London, UK.
authors: Stephen E
authors: SE
authors: Moss
authors: Institute for Molecular Bioscience and Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, Queensland, Australia.
authors: Robert G
authors: RG
authors: Parton
authors: EMBL Australia Node in Single Molecule Science, School of Medical Science, University of New South Wales (UNSW), Sydney, New South Wales, Australia.|ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, New South Wales, Australia.
authors: Jérémie
authors: J
authors: Rossy
authors: EMBL Australia Node in Single Molecule Science, School of Medical Science, University of New South Wales (UNSW), Sydney, New South Wales, Australia.|ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, New South Wales, Australia.
authors: Katharina
authors: K
authors: Gaus
mesh_terms: D000818:Animals; D017317:Annexin A6 / Q000172:deficiency / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002784:Cholesterol / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism*; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*
chemical_list: D017317:Annexin A6; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor; D002784:Cholesterol