CD4+ T-cell dysfunctions through the impaired lipid rafts ameliorate concanavalin A-induced hepatitis in sphingomyelin synthase 1-knockout mice

International Immunology
Lingli DongHisanori Umehara

Abstract

Membrane microdomains consisting of sphingomyelin (SM) and cholesterol appear to be important for signal transduction in T-cell activation. The present study was designed to elucidate the role of membrane SM in vivo and in vitro using sphingomyelin synthase 1 (SMS1) knock out (SMS1(-/-)) mice and Concanavalin A (ConA)-induced hepatitis. After establishing SMS1(-/-) mice, we investigated CD4+ T-cell functions including proliferation, cytokine production and signal transduction in vivo. We also examined severity of hepatitis, cytokine production in serum and liver after ConA injection at a dose of 20 mg kg(-1). CD4+ T cells from SMS1(-/-) mice showed severe deficiency of membrane SM and several profound defects compared with wild-type controls as follows: (i) cellular proliferation and production of IL-2 and IFN-γ by co-cross-linking of CD3 and CD4; (ii) tyrosine phosphorylation of LAT and its association with ZAP-70; (iii) clustering and co-localization of TCR with lipid rafts. Consistent with these impaired CD4+ T-cell functions in vitro, SMS1(-/-) mice showed decreased serum levels of IL-6 and IFN-γ by ConA injection, which renders SMS1(-/-) mice less sensitive to ConA-induced hepatitis. These results indicated that the defici...Continue Reading

References

Jul 1, 1992·The Journal of Clinical Investigation·G TiegsA Wendel
Jun 5, 1997·Nature·K Simons, E Ikonen
Mar 28, 1998·The Journal of Biological Chemistry·A YamajiM Umeda
May 3, 2000·Proceedings of the National Academy of Sciences of the United States of America·K TakedaK Okumura
Sep 26, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·F NicolettiP Meroni
Feb 28, 2002·Annual Review of Immunology·Lawrence E Samelson
Sep 21, 2002·Cytokine·Gabriele SassGisa Tiegs
Mar 5, 2003·Annual Review of Immunology·Michelle DykstraSusan K Pierce
Apr 5, 2003·The Journal of Biological Chemistry·Akiko Yamaji-HasegawaToshihide Kobayashi
Sep 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Barbara JarugaBin Gao
Dec 20, 2003·The EMBO Journal·Klazien HuitemaJoost C M Holthuis
May 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fran BalamuthKim Bottomly
May 14, 2004·Annual Review of Biophysics and Biomolecular Structure·Kai Simons, Winchil L C Vaz
May 18, 2004·Trends in Immunology·Daniel M Davis, Michael L Dustin
Jun 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takeshi SaitoSatoshi Yamagoe
Jan 26, 2005·Trends in Immunology·William RodgersSudha Mishra
Apr 21, 2005·The Journal of Biological Chemistry·Etsuko KiyokawaToshihide Kobayashi
Jul 13, 2005·The Journal of Experimental Medicine·Michihiko MiyajiHisanori Umehara
Apr 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ori WaldAmnon Peled
Aug 2, 2006·Biological & Pharmaceutical Bulletin·Toshihide KobayashiYoshio Hirabayashi
Jan 3, 2007·Nature Cell Biology·Ken JacobsonRichard G W Anderson
Apr 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ren ZhuAndré Herbelin
Jul 21, 2007·Science·Edward F DeLong
Mar 29, 2008·The Biochemical Journal·Maristella VillaniChiara Luberto
Oct 22, 2008·FEBS Letters·Panagiotis S Kabouridis, Elizabeth C Jury
Jan 2, 2010·Science·Daniel Lingwood, Kai Simons

❮ Previous
Next ❯

Citations

Oct 19, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Mary G Sorci-Thomas, Michael J Thomas
Jul 25, 2015·Translational Research : the Journal of Laboratory and Clinical Medicine·Francine K WeltyTarec K Elajami
Jul 19, 2013·Biochimica Et Biophysica Acta·Mitsuhiro Abe, Toshihide Kobayashi
Mar 5, 2016·Pharmacological Reports : PR·Kamil BieniasHalina Car
Nov 26, 2014·Alcoholism, Clinical and Experimental Research·Ningfeng TangCynthia F Bearer
Jul 11, 2016·Cell Biology and Toxicology·Guiying JinQing Yang
Oct 28, 2016·PloS One·Anke WittmannThomas Floss
Dec 19, 2018·International Immunology·Kaoru ToshimaJin-Ichi Inokuchi
May 20, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Toshio OhnishiToshiro Okazaki
Oct 3, 2018·International Journal of Molecular Medicine·Panpan ZhangNianlong Yan
Sep 7, 2018·Proceedings of the National Academy of Sciences of the United States of America·Govind KunduriJairaj K Acharya
Mar 21, 2019·Clinical Science·Zemou YuYining Huang
Jun 20, 2019·International Journal of Molecular Sciences·Lingyue HuaNianlong Yan
Oct 8, 2020·Journal of Lipid and Atherosclerosis·Makoto Taniguchi, Toshiro Okazaki
Aug 22, 2021·Cellular Signalling·Makoto Taniguchi, Toshiro Okazaki

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.