Pathogenesis of human systemic lupus erythematosus: recent advances

被引:264
作者
Crispin, Jose C. [1 ]
Liossis, Stamatis-Nick C. [2 ]
Kis-Toth, Katalin [1 ]
Lieberman, Linda A. [1 ]
Kyttaris, Vasileios C. [1 ]
Juang, Yuang-Taung [1 ]
Tsokos, George C. [1 ]
机构
[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Rheumatol, Boston, MA 02115 USA
[2] Univ Patras, Sch Med, Patras Univ Hosp, Dept Med,Div Rheumatol, GR-26110 Patras, Greece
关键词
EPSTEIN-BARR-VIRUS; PLASMACYTOID DENDRITIC CELLS; SUPPRESSES IL-2 PRODUCTION; PROTEIN PHOSPHATASE 2A; INNATE IMMUNE-RESPONSE; T-CELLS; DISEASE-ACTIVITY; DNA METHYLATION; PRONE MICE; FUNCTIONAL VARIANTS;
D O I
10.1016/j.molmed.2009.12.005
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
Systemic lupus erythematosus (SLE) is an autoimmune disease with manifestations derived from the involvement of multiple organs including the kidneys, joints, nervous system and hematopoietic organs. Immune system aberrations, as well as heritable, hormonal and environmental factors interplay in the expression of organ damage. Recent contributions from different fields have developed our understanding of SLE and reshaped current pathogenic models. Here, we review recent findings that deal with (i) genes associated with disease expression; (ii) immune cell molecular abnormalities that lead to autoimmune pathology; (iii) the role of hormones and sex chromosomes in the development of disease; and (iv) environmental and epigenetic factors thought to contribute to the expression of SLE. Finally, we highlight molecular defects intimately associated with the disease process of SLE that might represent ideal therapeutic targets and disease biomarkers.
引用
收藏
页码:47 / 57
页数:11
相关论文
共 141 条
[21]   Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection [J].
Cornall, RJ ;
Cyster, JG ;
Hibbs, ML ;
Dunn, AR ;
Otipoby, KL ;
Clark, EA ;
Goodnow, CC .
IMMUNITY, 1998, 8 (04) :497-508
[22]   Immunoregulatory T cells in autoimmunity [J].
Crispin, JC ;
Vargas, MI ;
Alcocer-Varela, J .
AUTOIMMUNITY REVIEWS, 2004, 3 (02) :135-141
[23]  
CRISPIN JC, 2003, ARTHRITIS R IN PRESS
[24]   How signals and gene transcription aberrations dictate the systemic lupus erythematosus T cell phenotype [J].
Crispin, Jose C. ;
Kyttaris, Vasileios C. ;
Juang, Vuang-Taung ;
Tsokos, George C. .
TRENDS IN IMMUNOLOGY, 2008, 29 (03) :110-115
[25]   Human TCR-αβ+ CD4- CD8- T Cells Can Derive from CD8+ T Cells and Display an Inflammatory Effector Phenotype [J].
Crispin, Jose C. ;
Tsokos, George C. .
JOURNAL OF IMMUNOLOGY, 2009, 183 (07) :4675-4681
[26]   Expanded Double Negative T Cells in Patients with Systemic Lupus Erythematosus Produce IL-17 and Infiltrate the Kidneys [J].
Crispin, Jose C. ;
Oukka, Mohamed ;
Bayliss, George ;
Cohen, Robert A. ;
Van Beek, Christine A. ;
Stillman, Isaac E. ;
Kyttaris, Vasileios C. ;
Juang, Yuang-Taung ;
Tsokos, George C. .
JOURNAL OF IMMUNOLOGY, 2008, 181 (12) :8761-8766
[27]   Complement protein C1q induces maturation of human dendritic cells [J].
Csomor, Eszter ;
Bajtay, Zsuzsa ;
Sandor, Noemi ;
Kristof, Katalin ;
Arlaud, Gerard J. ;
Thiel, Steffen ;
Erdei, Anna .
MOLECULAR IMMUNOLOGY, 2007, 44 (13) :3389-3397
[28]   Normally occurring NKG2D+CD4+ T cells are immunosuppressive and inversely correlated with disease activity in juvenile-onset lupus [J].
Dai, Zhenpeng ;
Turtle, Cameron J. ;
Booth, Garrett C. ;
Riddell, Stanley R. ;
Gooley, Theodore A. ;
Stevens, Anne M. ;
Spies, Thomas ;
Groh, Veronika .
JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (04) :793-805
[29]   Nucleosome, the main autoantigen in systemic lupus erythematosus, induces direct dendritic cell activation via a MyD88-independent pathway:: Consequences on inflammation [J].
Decker, P ;
Singh-Jasuja, H ;
Haager, S ;
Kötter, I ;
Rammensee, HG .
JOURNAL OF IMMUNOLOGY, 2005, 174 (06) :3326-3334
[30]   Cholera toxin B accelerates disease progression in lupus-prone mice by promoting lipid raft aggregation [J].
Deng, Guo-Min ;
Tsokos, George C. .
JOURNAL OF IMMUNOLOGY, 2008, 181 (06) :4019-4026