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Clinical Reviews in Allergy & Immunology

, Volume 47, Issue 2, pp 136–147 | Cite as

TLR2 and TLR4 in Autoimmune Diseases: a Comprehensive Review

  • Yu Liu
  • Heng Yin
  • Ming Zhao
  • Qianjin LuEmail author
Article

Abstract

Autoimmune diseases are immune disorders characterized by T cell hyperactivity and B cell overstimulation leading to overproduction of autoantibodies. Although the pathogenesis of various autoimmune diseases remains to be elucidated, environmental factors have been thought to contribute to the initiation and maintenance of auto-respond inflammation. Toll-like receptors (TLRs) are pattern recognition receptors belonging to innate immunity that recognize and defend invading microorganisms. Besides these exogenous pathogen-associated molecular patterns, TLRs can also bind with damage-associated molecular patterns produced under strike or by tissue damage or cells apoptosis. It is believed that TLRs build a bridge between innate immunity and autoimmunity. There are five adaptors to TLRs including MyD88, TRIF, TIRAP/MAL, TRAM, and SARM. Upon activation, TLRs recruit specific adaptors to initiate the downstream signaling pathways leading to the production of inflammatory cytokines and chemokines. Under certain circumstances, ligation of TLRs drives to aberrant activation and unrestricted inflammatory responses, thereby contributing to the perpetuation of inflammation in autoimmune diseases. In the past, most studies focused on the intracellular TLRs, such as TLR3, TLR7, and TLR9, but recent studies reveal that cell surface TLRs, especially TLR2 and TLR4, also play an essential role in the development of autoimmune diseases and afford multiple therapeutic targets. In this review, we summarized the biological characteristics, signaling mechanisms of TLR2/4, the negative regulators of TLR2/4 pathway, and the pivotal function of TLR2/4 in the pathogenesis of autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren’s syndrome, psoriasis, multiple sclerosis, and autoimmune diabetes.

Keywords

TLR2 TLR4 Autoimmune diseases 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant no. 81220108017, no. 81373205, and no. 81270024), the Specialized Research Fund for the Doctoral Program of Higher Education (grant no. 20120162130003), and the Programs of Science-Technology Commission of Hunan province (2013FJ4202, 2011TP4019-7) and the Fundamental Research Funds for the Central Universities.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Dermatology, Second Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Hunan Key Laboratory of Medical EpigeneticsChangshaPeople’s Republic of China

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