Siglec-E is up-regulated and phosphorylated following lipopolysaccharide stimulation in order to limit TLR-driven cytokine production.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Caroline R BoydCaroline A Jefferies

Abstract

Although production of cytokines by TLR is essential for viral and bacterial clearance, overproduction can be detrimental, thus controlling these responses is essential. CD33-related sialic acid binding Ig-like lectin receptors (Siglecs) have been implicated in the control of leukocyte responses. In this study, we report that murine Siglec-E is induced by TLRs in a MyD88-specific manner, is tyrosine phosphorylated following LPS stimulation, and negatively regulates TLR responses. Specifically, we demonstrate the Siglec-E expression inhibits TLR-induced NF-kappaB and more importantly, the induction of the antiviral cytokines IFN-beta and RANTES. Siglec-E mediates its inhibitory effects on TIR domain containing adaptor inducing IFN-beta (TRIF)-dependent cytokine production via recruitment of the tyrosine [corrected] phosphatase SHP2 and subsequent inhibition of TBK1 activity as evidenced by enhanced TBK1 phosphorylation in cells following knockdown of Siglec-E expression. Taken together, our results demonstrate a novel role for Siglec-E in controlling the antiviral response to TLRs and thus helping to maintain a healthy cytokine balance following infection.

References

Aug 2, 2002·Cell·Koichi KobayashiRichard A Flavell
Apr 15, 2003·Nature Immunology·Katherine A FitzgeraldTom Maniatis
Dec 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Sarah M McWhirterTom Maniatis
Dec 31, 2003·The Journal of Biological Chemistry·James F BurrowsJames A Johnston
Dec 14, 2004·Immunity·Gretchen E DiehlAstar Winoto
Feb 7, 2006·Trends in Immunology·Robert J Salmond, Denis R Alexander
Dec 2, 2006·The Journal of Biological Chemistry·Selinda J OrrJames A Johnston
Jan 26, 2007·Journal of Virology·Joanne ElliottJames A Johnston
Mar 24, 2007·Nature Reviews. Immunology·Paul R CrockerAjit Varki
Aug 29, 2007·The Journal of Experimental Medicine·Younghwa KimAihao Ding
Mar 8, 2008·Biochemical and Biophysical Research Communications·Munetoshi AndoShinji Iijima
Jul 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rowan HiggsCaroline A Jefferies
Jul 23, 2008·The Journal of Experimental Medicine·Maciej LechHans-Joachim Anders
Aug 19, 2008·Cytokine·Elaine F Kenny, Luke A J O'Neill
Nov 13, 2008·The Journal of Allergy and Clinical Immunology·Andrew H Liu

❮ Previous
Next ❯

Citations

Sep 23, 2014·Nature Reviews. Immunology·Matthew S MacauleyJames C Paulson
Jan 10, 2012·Annual Review of Immunology·Shiv PillaiHamid Mattoo
Dec 24, 2010·Journal of Innate Immunity·Norihito KawasakiJames C Paulson
Feb 26, 2011·Nature Reviews. Immunology·George Hajishengallis, John D Lambris
Jun 28, 2011·The Journal of Biological Chemistry·Svetislav S ZaricClifford C Taggart
Nov 15, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Janine ClaudeHarald Neumann
Nov 6, 2015·Bioscience, Biotechnology, and Biochemistry·Hiroshi HiguchiKen-ichi Nishijima
Mar 1, 2016·Bioscience, Biotechnology, and Biochemistry·Hiroshi HiguchiKen-Ichi Nishijima
Sep 4, 2015·Science Translational Medicine·Shaun SpenceChristopher J Scott
Jul 13, 2013·Immunological Investigations·Li-Xin ZhangJun-xing Huang
Dec 7, 2017·Frontiers in Immunology·Yan-Cun LiuSong-Tao Shou
Mar 6, 2018·Cellular & Molecular Immunology·Rhonda FloresYang Liu
Dec 24, 2015·Current Opinion in Allergy and Clinical Immunology·Robert P SchleimerBruce S Bochner
Sep 25, 2019·Cells·Shoib Sarwar SiddiquiHussain Al Zouabi
Mar 17, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paula C SotoAjit Varki
Feb 1, 2012·Annals of the New York Academy of Sciences·James C PaulsonNorihito Kawasaki
Feb 23, 2012·Annals of the New York Academy of Sciences·Paul R CrockerHannah E Richards
Jul 30, 2020·Cellular and Molecular Life Sciences : CMLS·Hauke ThieslerHerbert Hildebrandt
Sep 2, 2017·Scientific Reports·Zhilin ZengJungang Xie
Apr 10, 2014·Cytotechnology·Toru ShojiShinji Iijima
Sep 14, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yin WuGuo-Yun Chen
Nov 13, 2018·Frontiers in Immunology·Urban Švajger, Primož Rožman
Sep 17, 2019·Expert Opinion on Therapeutic Targets·Anne Bärenwaldt, Heinz Läubli
Oct 26, 2016·Microbiology Spectrum·Gordon D Brown, Paul R Crocker
Jun 22, 2021·Annual Review of Cell and Developmental Biology·Spencer Freeman, Sergio Grinstein
Jan 28, 2022·The Journal of Pathology. Clinical Research·Xianlong ChenJie Chen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.