Sec13 Regulates Expression of Specific Immune Factors Involved in Inflammation In Vivo

Thais G. Moreira, Liang Zhang, Lihi Shaulov, Amnon Harel, Sharon K. Kuss, Jessica Williams, John Shelton, Bandarigoda Somatilaka, Joachim Seemann, Jue Yang, Ramanavelan Sakthivel, Daniel R. Nussenzveig, Ana M C Faria, Beatriz M A Fontoura

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 (Sec13H/-) 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 Sec13H/- 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.

Original languageEnglish (US)
Article number17655
JournalScientific Reports
Volume5
DOIs
StatePublished - Dec 3 2015

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Immunologic Factors
Inflammation
COP-Coated Vesicles
T-Lymphocytes
Nuclear Pore
Immunosuppressive Agents
Interleukin-4
Immunoglobulins
Immunization
Interleukin-6
Anatomy
B-Lymphocytes
Macrophages
Membranes
Serum
Proteins

ASJC Scopus subject areas

  • General

Cite this

Sec13 Regulates Expression of Specific Immune Factors Involved in Inflammation In Vivo. / Moreira, Thais G.; Zhang, Liang; Shaulov, Lihi; Harel, Amnon; Kuss, Sharon K.; Williams, Jessica; Shelton, John; Somatilaka, Bandarigoda; Seemann, Joachim; Yang, Jue; Sakthivel, Ramanavelan; Nussenzveig, Daniel R.; Faria, Ana M C; Fontoura, Beatriz M A.

In: Scientific Reports, Vol. 5, 17655, 03.12.2015.

Research output: Contribution to journalArticle

Moreira, TG, Zhang, L, Shaulov, L, Harel, A, Kuss, SK, Williams, J, Shelton, J, Somatilaka, B, Seemann, J, Yang, J, Sakthivel, R, Nussenzveig, DR, Faria, AMC & Fontoura, BMA 2015, 'Sec13 Regulates Expression of Specific Immune Factors Involved in Inflammation In Vivo', Scientific Reports, vol. 5, 17655. https://doi.org/10.1038/srep17655
Moreira TG, Zhang L, Shaulov L, Harel A, Kuss SK, Williams J et al. Sec13 Regulates Expression of Specific Immune Factors Involved in Inflammation In Vivo. Scientific Reports. 2015 Dec 3;5. 17655. https://doi.org/10.1038/srep17655
Moreira, Thais G. ; Zhang, Liang ; Shaulov, Lihi ; Harel, Amnon ; Kuss, Sharon K. ; Williams, Jessica ; Shelton, John ; Somatilaka, Bandarigoda ; Seemann, Joachim ; Yang, Jue ; Sakthivel, Ramanavelan ; Nussenzveig, Daniel R. ; Faria, Ana M C ; Fontoura, Beatriz M A. / Sec13 Regulates Expression of Specific Immune Factors Involved in Inflammation In Vivo. In: Scientific Reports. 2015 ; Vol. 5.
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