MicroRNA21 Meets Neuronal TLR8: Non-canonical Functions of MicroRNA in Neuropathic Pain

  • Zhi-Hong Wang
  • Tong LiuEmail author

Toll-like receptors (TLRs) are well-known as pattern-recognition receptors in the immune system for recognizing pathogen-associated and damage-associated molecular patterns [1]. TLRs play an essential role in the innate and adaptive immune responses. To date, 10 functional TLRs have been identified in humans (TLR1–TLR10) and 12 in mice (TLR1–TLR9 and TLR11–TLR13) [1]. TLRs are evolutionarily conserved type I transmembrane proteins and comprise an ectodomain characterized by leucine-rich repeats mediating the recognition of ligands, a transmembrane region, and cytosolic Toll-interleukin (IL)-1 receptor domains that activate the downstream signaling pathways [1]. Most types of TLRs form homodimers between themselves, but certain TLRs can also form heterodimers, such as TLR1/TLR2 and TLR2/TLR6. The adaptor protein MyD88 is required for the downstream signaling of most TLRs, but not for TLR3 signaling. The adaptor protein TRIF (TIR-domain-containing adapter-inducing interferon-β) is used...



We thank Prof. Yong-Jing Gao for critical reading of the manuscript. Tong Liu was supported by grants from the National Natural Science Foundation of China (81870874, 31371179, and 81300968) and the Natural Science Foundation of Jiangsu Province, China (BK20170004 and 2015-JY-029).


  1. 1.
    Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on toll-like receptors. Nat Immunol 2010, 11: 373–384.CrossRefGoogle Scholar
  2. 2.
    Hanke ML, Kielian T. Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Clin Sci (Lond) 2011, 121: 367–387.CrossRefGoogle Scholar
  3. 3.
    Liu T, Gao YJ, Ji RR. Emerging role of Toll-like receptors in the control of pain and itch. Neurosci Bull 2012, 28: 131–144.CrossRefGoogle Scholar
  4. 4.
    Tsuda M. Modulation of pain and itch by spinal glia. Neurosci Bull 2018, 34: 178–185.CrossRefGoogle Scholar
  5. 5.
    Park CK, Xu ZZ, Berta T, Han Q, Chen G, Liu XJ, et al. Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1. Neuron 2014, 82: 47–54.CrossRefGoogle Scholar
  6. 6.
    Liu T, Han Q, Chen G, Huang Y, Zhao LX, Berta T, et al. Toll-like receptor 4 contributes to chronic itch, alloknesis, and spinal astrocyte activation in male mice. Pain 2016, 157: 806–817.CrossRefGoogle Scholar
  7. 7.
    Zhang ZJ, Guo JS, Li SS, Wu XB, Cao DL, Jiang BC, et al. TLR8 and its endogenous ligand miR-21 contribute to neuropathic pain in murine DRG. J Exp Med 2018, 215: 3019–3037.CrossRefGoogle Scholar
  8. 8.
    Liu T, Xu ZZ, Park CK, Berta T, Ji RR. Toll-like receptor 7 mediates pruritus. Nat Neurosci 2010, 13: 1460–1462.CrossRefGoogle Scholar
  9. 9.
    Ma Y, Li J, Chiu I, Wang Y, Sloane JA, Lu J, et al. Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis. J Cell Biol 2006, 175: 209–215.CrossRefGoogle Scholar
  10. 10.
    Han Q, Liu D, Convertino M, Wang Z, Jiang C, Kim YH, et al. miRNA-711 binds and activates TRPA1 extracellularly to evoke acute and chronic pruritus. Neuron 2018, 99: 449–463 e446.CrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  1. 1.Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of NeuroscienceSoochow UniversitySuzhouChina
  2. 2.College of Life SciencesYanan UniversityYananChina

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