FcγRIIIa-Syk Co-signal Modulates CD4+ T-cell Response and Up-regulates Toll-like Receptor (TLR) Expression

被引:13
作者
Chauhan, Anil K. [1 ]
Moore, Terry L. [1 ]
Bi, Ye [1 ]
Chen, Chen [1 ]
机构
[1] St Louis Univ, Sch Med, Div Adult & Pediat Rheumatol, 1402 South Grand Blvd, St Louis, MO 63104 USA
基金
美国国家卫生研究院;
关键词
SYSTEMIC-LUPUS-ERYTHEMATOSUS; INTERFERON-GAMMA; IMMUNE-COMPLEXES; HELPER-CELLS; COSTIMULATORY MOLECULES; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; GERMINAL-CENTERS; TYROSINE KINASE; DENDRITIC CELLS;
D O I
10.1074/jbc.M115.684795
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
CD4(+) T-cells in systemic lupus erythematosus (SLE) patients show altered T-cell receptor signaling, which utilizes Fc-receptor gamma-chain FcR gamma-Syk. A role for Fc gamma RIIIa activation from immune complex (IC) ligation and sublytic terminal complement complex (C5b-9) in CD4(+) T-cell responses is not investigated. In this study, we show that the ICs present in SLE patients by ligating to Fc gamma RIIIa on CD4(+) T-cells phosphorylate Syk and provide a co-stimulatory signal to CD4(+) T-cells in the absence of CD28 signal. This led to the development of pathogenic IL-17A(+) and IFN-gamma(high) CD4(+) T-cells in vitro. Cytokines IL-1 beta, IL-6, TGF-beta 1, and IL-23 were the only requirement for the development of both populations. SLE patients CD4(+) T-cells that expressed CD25, CD69, and CD98 bound to ICs showed pSyk and produced IFN-gamma and IL-17A. This Fc gamma RIIIa-mediated co-signal differentially up-regulated the expression of IFN pathway genes compared with CD28 co-signal. Fc gamma RIIIa-pSyk upregulated several toll-like receptor genes as well as the HMGB1 and MyD88 gene transcripts. ICs co-localized with these toll-like receptor pathway proteins. These results suggest a role for the Fc gamma RIIIa-pSyk signal in modulating adaptive immune responses.
引用
收藏
页码:1368 / 1386
页数:19
相关论文
共 87 条
  • [1] The role of positive costimulatory molecules in transplantation and tolerance
    Agarwal, Avinash
    Newell, Kenneth A.
    [J]. CURRENT OPINION IN ORGAN TRANSPLANTATION, 2008, 13 (04) : 366 - 372
  • [2] Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17
    Aggarwal, S
    Ghilardi, N
    Xie, MH
    de Sauvage, FJ
    Gurney, AL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) : 1910 - 1914
  • [3] IL-17 Promotes Murine Lupus
    Amarilyo, Gil
    Lourenco, Elaine V.
    Shi, Fu-Dong
    La Cava, Antonio
    [J]. JOURNAL OF IMMUNOLOGY, 2014, 193 (02) : 540 - 543
  • [4] Type 17 T helper cells-origins, features and possible roles in rheumatic disease
    Annunziato, Francesco
    Cosmi, Lorenzo
    Liotta, Francesco
    Maggi, Enrico
    Romagnani, Sergio
    [J]. NATURE REVIEWS RHEUMATOLOGY, 2009, 5 (06) : 325 - 331
  • [5] Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus
    Baechler, EC
    Batliwalla, FM
    Karypis, G
    Gaffney, PM
    Ortmann, WA
    Espe, KJ
    Shark, KB
    Grande, WJ
    Hughes, KM
    Kapur, V
    Gregersen, PK
    Behrens, TW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (05) : 2610 - 2615
  • [6] Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA
    Barton, GM
    Kagan, JC
    Medzhitov, R
    [J]. NATURE IMMUNOLOGY, 2006, 7 (01) : 49 - 56
  • [7] TH-17 cells in the circle of immunity and autoimmunity
    Bettelli, Estelle
    Oukka, Mohamed
    Kuchroo, Vijay K.
    [J]. NATURE IMMUNOLOGY, 2007, 8 (04) : 345 - 350
  • [8] Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/B7 family
    Bour-Jordan, Helene
    Esensten, Jonathan H.
    Martinez-Llordella, Marc
    Penaranda, Cristina
    Stumpf, Melanie
    Bluestone, Jeffrey A.
    [J]. IMMUNOLOGICAL REVIEWS, 2011, 241 : 180 - 205
  • [9] A Regulatory Role for IL-10 Receptor Signaling in Development and B Cell Help of T Follicular Helper Cells in Mice
    Cai, Gang
    Nie, Xiaomeng
    Zhang, Weiwei
    Wu, Beiying
    Lin, Jiafei
    Wang, Huaizhou
    Jiang, Cen
    Shen, Qian
    [J]. JOURNAL OF IMMUNOLOGY, 2012, 189 (03) : 1294 - 1302
  • [10] Direct stimulation of human T cells via TLR5 and TLR7/8:: Flagellin and R-848 up-regulate proliferation and IFN-γ production by memory CD4+ T cells
    Caron, G
    Duluc, D
    Frémaux, I
    Jeannin, P
    David, C
    Gascan, H
    Delneste, Y
    [J]. JOURNAL OF IMMUNOLOGY, 2005, 175 (03) : 1551 - 1557