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TLR2 and TLR4 in Autoimmune Diseases: a Comprehensive Review

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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.

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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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  1. Department of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Rd, Changsha, Hunan, 410011, People’s Republic of China

    Yu Liu, Heng Yin, Ming Zhao & Qianjin Lu

  2. Hunan Key Laboratory of Medical Epigenetics, Changsha, Hunan, 410011, People’s Republic of China

    Yu Liu, Heng Yin, Ming Zhao & Qianjin Lu

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  1. Yu Liu
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  2. Heng Yin
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  3. Ming Zhao
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Correspondence to Qianjin Lu.

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Liu, Y., Yin, H., Zhao, M. et al. TLR2 and TLR4 in Autoimmune Diseases: a Comprehensive Review. Clinic Rev Allerg Immunol 47, 136–147 (2014). https://doi.org/10.1007/s12016-013-8402-y

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