Modulation of toll-like receptor function has therapeutic potential in autoimmune disease

被引:23
作者
Clanchy, Felix I. L. [1 ]
Sacre, Sandra M. [2 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Kennedy Inst Rheumatol Div, Fac Med, London W6 8LH, England
[2] Univ Sussex, Trafford Ctr, Brighton & Sussex Med Sch, Falmer BN1 9RY, E Sussex, England
关键词
autoimmune disease; inflammation; multiple sclerosis; murine models; rheumatoid arthritis; systemic lupus erythematosus; therapeutic targeting; TLR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLLAGEN-INDUCED ARTHRITIS; BLOOD MONONUCLEAR-CELLS; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; OLIGODENDROCYTE PROGENITOR MATURATION; PLASMACYTOID DENDRITIC CELLS; DEPENDENT SIGNALING PATHWAY; SYNOVIAL TISSUE MACROPHAGES; AUTOREACTIVE B-CELLS;
D O I
10.1517/14712598.2010.534080
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Importance of the field: The role of toll-like receptors (TLRs) in the immune response to exogenous pathogens is well characterized. These receptors have been suggested to be involved in the initiation and/or perpetuation of many inflammatory autoimmune diseases and have become attractive candidates for the modulation of inflammation. Areas covered in this review: This review discusses the evidence to support a potential role for TLRs in inflammatory diseases, focusing on rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. The approaches to targeting TLR activation are outlined. What the reader will gain: An appreciation for the role of TLRs in inflammatory diseases and in particular the contribution of specific TLRs in rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. This review focuses on recent developments in targeting TLR activity from ligand binding through to the resultant signaling. Take home message: As initiators of immune responses, TLRs have previously been targeted to increase the immune response with some success. However, targeting TLRs to attenuate immune responses for the treatment of chronic inflammatory diseases will require further evidence of the mechanisms of TLR involvement in the pathophysiology and a better understanding of the potential effects of modulating TLR physiology over a sustained period.
引用
收藏
页码:1703 / 1716
页数:14
相关论文
共 166 条
[121]   Impaired early B cell tolerance in patients with rheumatoid arthritis [J].
Samuels, J ;
Ng, YS ;
Coupillaud, C ;
Paget, D ;
Meffre, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (10) :1659-1667
[122]   Polymorphisms of toll-like receptor 2 and 4 genes in rheumatoid arthritis and systemic lupus erythematosus [J].
Sánchez, E ;
Orozco, G ;
López-Nevot, MA ;
Jiménez-Alonso, J ;
Martín, J .
TISSUE ANTIGENS, 2004, 63 (01) :54-57
[123]   Requirement of toll-like receptor 7 for pristane-induced production of autoantibodies and development of murine lupus nephritis [J].
Savarese, Emina ;
Steinberg, Christian ;
Pawar, Rahul D. ;
Reindl, Wolfgang ;
Akira, Shizuo ;
Anders, Hans-Joachim ;
Krug, Anne .
ARTHRITIS AND RHEUMATISM, 2008, 58 (04) :1107-1115
[124]   Enhanced expression of heat shock protein 70 (hsp70) and heat shock factor 1 (HSF1) activation in rheumatoid arthritis synovial tissue -: Differential regulation of hsp70 expression and HSF1 activation in synovial fibroblasts by proinflammatory cytokines, shear stress, and antiinflammatory drugs [J].
Schett, G ;
Redlich, K ;
Xu, QB ;
Bizan, P ;
Gröger, M ;
Tohidast-Akrad, M ;
Kiener, H ;
Smolen, J ;
Steiner, G .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (02) :302-311
[125]   IKKβ inhibition protects against bone and cartilage destruction in a rat model of rheumatoid arthritis [J].
Schopf, Lisa ;
Savinainen, Anneli ;
Anderson, Karen ;
Kujawa, Julie ;
DuPont, Michelle ;
Silva, Matthew ;
Siebert, Elizabeth ;
Chandra, Sudeep ;
Morgan, Jennifer ;
Gangurde, Pranoti ;
Wen, Danyi ;
Lane, Joan ;
Xu, Yajun ;
Hepperle, Michael ;
Harriman, Geraldine ;
Ocain, Timothy ;
Jaffee, Bruce .
ARTHRITIS AND RHEUMATISM, 2006, 54 (10) :3163-3173
[126]   Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis [J].
Schrijver, IA ;
van Meurs, M ;
Melief, MJ ;
Ang, CW ;
Buljevac, D ;
Ravid, R ;
Hazenberg, MP ;
Laman, JD .
BRAIN, 2001, 124 :1544-1554
[127]  
Schumacher HR, 1999, ARTHRITIS RHEUM-US, V42, P1281, DOI 10.1002/1529-0131(199906)42:6<1281::AID-ANR27>3.0.CO
[128]  
2-8
[129]  
SCOTT DL, 1981, BRIT J EXP PATHOL, V62, P362
[130]   CPG oligonucleotides are potent adjuvants for the activation of autoreactive encephalitogenic T cells in vivo [J].
Segal, BM ;
Chang, JT ;
Shevach, EM .
JOURNAL OF IMMUNOLOGY, 2000, 164 (11) :5683-5688