title: Disruption of Serinc1, which facilitates serine-derived lipid synthesis, fails to alter macrophage function, lymphocyte proliferation or autoimmune disease susceptibility.
abstract: During immune cell activation, serine-derived lipids such as phosphatidylserine and sphingolipids contribute to the formation of protein signaling complexes within the plasma membrane. Altering lipid composition in the cell membrane can subsequently affect immune cell function and the development of autoimmune disease. Serine incorporator 1 (SERINC1) is a putative carrier protein that facilitates synthesis of serine-derived lipids. To determine if SERINC1 has a role in immune cell function and the development of autoimmunity, we characterized a mouse strain in which a retroviral insertion abolishes expression of the Serinc1 transcript. Expression analyses indicated that the Serinc1 transcript is readily detectable and expressed at relatively high levels in wildtype macrophages and lymphocytes. The ablation of Serinc1 expression in these immune cells, however, did not significantly alter serine-derived lipid composition or affect macrophage function and lymphocyte proliferation. Analyses of Serinc1-deficient mice also indicated that systemic ablation of Serinc1 expression did not affect viability, fertility or autoimmune disease susceptibility. These results suggest that Serinc1 is dispensable for certain immune cell functions and does not contribute to previously reported links between lipid composition in immune cells and autoimmunity.
authors.affiliation: St Vincent's Institute, Fitzroy, Victoria 3065, Australia; Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia.
authors.forename: Edward P F
authors.initials: EP
authors.lastname: Chu
authors.affiliation: St Vincent's Institute, Fitzroy, Victoria 3065, Australia.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Elso
authors.affiliation: European Molecular Biology Laboratory (EMBL) Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Abigail H
authors.initials: AH
authors.lastname: Pollock
authors.affiliation: St Vincent's Institute, Fitzroy, Victoria 3065, Australia; Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia.
authors.forename: May A
authors.initials: MA
authors.lastname: Alsayb
authors.affiliation: St Vincent's Institute, Fitzroy, Victoria 3065, Australia.
authors.forename: Leanne
authors.initials: L
authors.lastname: Mackin
authors.affiliation: St Vincent's Institute, Fitzroy, Victoria 3065, Australia; Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Thomas
authors.affiliation: St Vincent's Institute, Fitzroy, Victoria 3065, Australia; Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia.
authors.forename: Thomas W H
authors.initials: TW
authors.lastname: Kay
authors.affiliation: ANZAC Research Institute, Sydney, New South Wales 2139, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Silveira
authors.affiliation: Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia; Department of Molecular and Translational Science, Monash University, Melbourne, Victoria 3168, Australia.
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Mansell
authors.affiliation: European Molecular Biology Laboratory (EMBL) Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Katharina
authors.initials: K
authors.lastname: Gaus
authors.affiliation: St Vincent's Institute, Fitzroy, Victoria 3065, Australia; Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia. Electronic address: tbrodnicki@svi.edu.au.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Brodnicki
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology*; D005434:Flow Cytometry; D050356:Lipid Metabolism / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012694:Serine / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C406670:Tde2 protein, mouse; D012694:Serine
keywords: Autoimmune disease; Lymphocytes; Macrophages; Membrane lipid biosynthesis; Phosphatidylserine; Sphingolipids