title: IFT20 controls LAT recruitment to the immune synapse and T-cell activation in vivo.
abstract: Biogenesis of the immune synapse at the interface between antigen-presenting cells and T cells assembles and organizes a large number of membrane proteins required for effective signaling through the T-cell receptor. We showed previously that the intraflagellar transport protein 20 (IFT20), a component of the intraflagellar transport system, controls polarized traffic during immune synapse assembly. To investigate the role of IFT20 in primary CD4(+) T cells in vitro and in vivo, we generated mice bearing a conditional defect of IFT20 expression in T cells. We show that in the absence of IFT20, although cell spreading and the polarization of the centrosome were unaffected, T-cell receptor (TCR)-mediated signaling and recruitment of the signaling adaptor LAT (linker for activation of T cells) at the immune synapse were reduced. As a consequence, CD4(+) T-cell activation and proliferation were also defective. In vivo, conditional IFT20-deficient mice failed to mount effective antigen-specific T-cell responses, and their T cells failed to induce colitis after adoptive transfer to Rag(-/-) mice. IFT20 is therefore required for the delivery of the intracellular pool of LAT to the immune synapse in naive primary T lymphocytes and for effective T-cell responses in vivo.
authors.affiliation: Institut Curie, Paris Sciences et Lettres (PSL) Research University, INSERM, Unité 932, Immunité et Cancer, Paris, F-75248, France;
authors.forename: Omar I
authors.initials: OI
authors.lastname: Vivar
authors.affiliation: Department of Life Sciences, University of Siena, 53100 Siena, Italy;
authors.forename: Giulia
authors.initials: G
authors.lastname: Masi
authors.affiliation: Institut Curie, Paris Sciences et Lettres (PSL) Research University, INSERM, Unité 932, Immunité et Cancer, Paris, F-75248, France; Université Paris Descartes, Sorbonne Paris Cité, F-75005, Paris, France;
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Carpier
authors.affiliation: Institut Curie, Paris Sciences et Lettres (PSL) Research University, INSERM, Unité 932, Immunité et Cancer, Paris, F-75248, France;
authors.forename: Joao G
authors.initials: JG
authors.lastname: Magalhaes
authors.affiliation: Department of Life Sciences, University of Siena, 53100 Siena, Italy;
authors.forename: Donatella
authors.initials: D
authors.lastname: Galgano
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Pazour
authors.affiliation: Institut Curie, Paris Sciences et Lettres (PSL) Research University, INSERM, Unité 932, Immunité et Cancer, Paris, F-75248, France; cosima.baldari@unisi.it sebastian.amigorena@curie.fr claire.hivroz@curie.fr.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Amigorena
authors.affiliation: Institut Curie, Paris Sciences et Lettres (PSL) Research University, INSERM, Unité 932, Immunité et Cancer, Paris, F-75248, France; cosima.baldari@unisi.it sebastian.amigorena@curie.fr claire.hivroz@curie.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Hivroz
authors.affiliation: Department of Life Sciences, University of Siena, 53100 Siena, Italy; cosima.baldari@unisi.it sebastian.amigorena@curie.fr claire.hivroz@curie.fr.
authors.forename: Cosima T
authors.initials: CT
authors.lastname: Baldari
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D015151:Immunoblotting; D054992:Immunological Synapses / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D060168:Thymocytes / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C487991:IFT20 protein, human; C514104:Ift20 protein, mouse; C110810:LAT protein, human; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell
keywords: CD4+ T cell; adoptive transfer; colitis; intraflagellar transport; vesicular traffic