title: Sec13 Regulates Expression of Specific Immune Factors Involved in Inflammation In Vivo.
abstract: The Sec13 protein functions in various intracellular compartments including the nuclear pore complex, COPII-coated vesicles, and inside the nucleus as a transcription regulator. Here we developed a mouse model that expresses low levels of Sec13 (Sec13(H/-)) to assess its functions in vivo, as Sec13 knockout is lethal. These Sec13 mutant mice did not present gross defects in anatomy and physiology. However, the reduced levels of Sec13 in vivo yielded specific immunological defects. In particular, these Sec13 mutant mice showed low levels of MHC I and II expressed by macrophages, low levels of INF-γ and IL-6 expressed by stimulated T cells, and low frequencies of splenic IFN-γ+CD8+ T cells. In contrast, the levels of soluble and membrane-bound TGF-β as well as serum immunoglobulin production are high in these mice. Furthermore, frequencies of CD19+CD5-CD95+ and CD19+CD5-IL-4+ B cells were diminished in Sec13(H/-) mice. Upon stimulation or immunization, some of the defects observed in the naïve mutant mice were compensated. However, TGF-β expression remained high suggesting that Sec13 is a negative modulator of TGF-β expression and of its immunosuppressive functions on certain immune cells. In sum, Sec13 regulates specific expression of immune factors with key functions in inflammation.
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.|Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil 31270-901.
authors.forename: Thais G
authors.initials: TG
authors.lastname: Moreira
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel.
authors.forename: Lihi
authors.initials: L
authors.lastname: Shaulov
authors.affiliation: Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel.
authors.forename: Amnon
authors.initials: A
authors.lastname: Harel
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Kuss
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Williams
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: John
authors.initials: J
authors.lastname: Shelton
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: Bandarigoda
authors.initials: B
authors.lastname: Somatilaka
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: Joachim
authors.initials: J
authors.lastname: Seemann
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: Jue
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: Ramanavelan
authors.initials: R
authors.lastname: Sakthivel
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.|Veterans Affairs North Texas Health Care System: Dallas VA Medical Center, Dallas, TX 75216, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Nussenzveig
authors.affiliation: Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil 31270-901.
authors.forename: Ana M C
authors.initials: AM
authors.lastname: Faria
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: Beatriz M A
authors.initials: BM
authors.lastname: Fontoura
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008817:Mice, Mutant Strains; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology
chemical_list: D002352:Carrier Proteins; D007155:Immunologic Factors; D015850:Interleukin-6; D009687:Nuclear Proteins; C000611521:Sec13 protein, mouse; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma