排序方式: 共有28条查询结果,搜索用时 156 毫秒
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Li Y Harada T Juang YT Kyttaris VC Wang Y Zidanic M Tung K Tsokos GC 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(3):1938-1947
Systemic lupus erythematosus (SLE) is an autoimmune/inflammatory disease characterized by autoantibody production and abnormal T cells that infiltrate tissues through not well-known mechanisms. We report that SLE T lymphocytes display increased levels of CD44, ezrin, radixin, and moesin (ERM) phosphorylation, stronger actin polymerization, higher polar cap formation, and enhanced adhesion and chemotactic migration compared with T cells from patients with rheumatoid arthritis and normal individuals. Silencing of CD44 by CD44 small interfering RNA in SLE T cells inhibited significantly their ability to adhere and migrate as did treatment with Rho kinase and actin polymerization inhibitors. Forced expression of T567D-ezrin, a phosphorylation-mimic form, enhanced remarkably the adhesion and migration rate of normal T cells. Anti-CD3/TCR autoantibodies present in SLE sera caused increased ERM phosphorylation, adhesion, and migration in normal T cells. pERM and CD44 are highly expressed in T cells infiltrating in the kidneys of patients with lupus nephritis. These data prove that increased ERM phosphorylation represents a key molecular abnormality that guides T cell adhesion and migration in SLE patients. 相似文献
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Kyttaris VC Juang YT Tenbrock K Weinstein A Tsokos GC 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(5):3557-3563
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Chatterjee M Rauen T Kis-Toth K Kyttaris VC Hedrich CM Terhorst C Tsokos GC 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(3):1206-1212
Altered T cell function in systemic lupus erythematosus (SLE) is determined by various molecular and cellular abnormalities, including increased IL-17 production. Recent evidence suggests a crucial role for signaling lymphocyte activation molecules (SLAMs) in the expression of autoimmunity. In this study, we demonstrate that SLAMF3 and SLAMF6 expression is increased on the surface of SLE T cells compared with normal cells. SLAM coengagement with CD3 under Th17 polarizing conditions results in increased IL-17 production. SLAMF3 and SLAMF6 T cell surface expression and IL-17 levels significantly correlate with disease activity in SLE patients. Both naive and memory CD4(+) T cells produce more IL-17 in response to SLAM costimulation as compared with CD28 costimulation. In naive CD4(+) cells, IL-17 production after CD28 costimulation peaks on day 3, whereas costimulation with anti-SLAMF3 and anti-SLAMF6 Abs results in a prolonged and yet increasing production during 6 d. Unlike costimulation with anti-CD28, SLAM costimulation requires the presence of the adaptor molecule SLAM-associated protein. Thus, engagement of SLAMF3 and SLAMF6 along with Ag-mediated CD3/TCR stimulation represents an important source of IL-17 production, and disruption of this interaction with decoy receptors or blocking Abs should mitigate disease expression in SLE and other autoimmune conditions. 相似文献
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Adults of the human parasitic trematode Schistosoma mansoni, which causes
hepatosplenic/intestinal complications in humans, synthesize
glycoconjugates containing the Lewis x (Lex) Galbeta1-->4(Fucalpha1--
>3)GlcNAcbeta1-->R, but not sialyl Lewis x (sLex), antigen. We now
report on our analyses of Lexand sLexexpression in S.haematobium and
S.japonicum, which are two other major species of human schistosomes that
cause disease, and the possible autoimmunity to these antigens in infected
individuals. Antigen expression was evaluated by both ELISA and Western
blot analyses of detergent extracts of parasites using monoclonal
antibodies. Several high molecular weight glycoproteins in both S.
haematobium and S. japonicum contain the Lexantigen, but no sialyl
Lexantigen was detected. In addition, sera from humans and rodents infected
with S.haematobium and S.japonicum contain antibodies reactive with Lex.
These results led us to investigate whether Lexantigens are expressed in
other helminths, including the parasitic trematode Fasciola hepatica , the
parasitic nematode Dirofilaria immitis (dog heartworm), the ruminant
nematode Haemonchus contortus , and the free-living nematode Caenorhabditis
elegans . Neither Lexnor sialyl-Lexis detectable in these other helminths.
Furthermore, none of the helminths, including schistosomes, express Lea,
Leb, Ley, or the H- type 1 antigen. However, several glycoproteins from all
helminths analyzed are bound by Lotus tetragonolobus agglutinin , which
binds Fucalpha1-->3GlcNAc, and Wisteria floribunda agglutinin, which
binds GalNAcbeta1-->4GlcNAc (lacdiNAc or LDN). Thus, schistosomes may be
unique among helminths in expressing the Lexantigen, whereas many different
helminths may express alpha1,3-fucosylated glycans and the LDN motif.
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Alexandros P. Grammatikos Debjani Ghosh Amy Devlin Vasileios C. Kyttaris George C. Tsokos 《PloS one》2013,8(8)
Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk is being considered as a therapeutic target we asked whether Syk is central to the multiple aberrantly modulated molecules in SLE T cells. Using a gene expression array, we demonstrate that forced expression of Syk in normal T cells reproduces most of the aberrantly expressed molecules whereas silencing of Syk in SLE T cells normalizes the expression of most abnormally expressed molecules. Protein along with gene expression modulation for select molecules was confirmed. Specifically, levels of cytokine IL-21, cell surface receptor CD44, and intracellular molecules PP2A and OAS2 increased following Syk overexpression in normal T cells and decreased after Syk silencing in SLE T cells. Our results demonstrate that levels of Syk affect the expression of a number of enzymes, cytokines and receptors that play a key role in the development of disease pathogenesis in SLE and provide support for therapeutic targeting in SLE patients. 相似文献