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NOD-like receptors in autoimmune diseases

Abstract

Autoimmune diseases are chronic immune diseases characterized by dysregulation of immune system, which ultimately results in a disruption in self-antigen tolerance. Cumulative data show that nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) play essential roles in various autoimmune diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, multiple sclerosis (MS), etc. NLR proteins, consisting of a C-terminal leucine-rich repeat (LRR), a central nucleotide-binding domain, and an N-terminal effector domain, form a group of pattern recognition receptors (PRRs) that mediate the immune response by specifically recognizing cellular pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) and triggering numerous signaling pathways, including RIP2 kinase, caspase-1, nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK) and so on. Based on their N-terminal domain, NLRs are divided into five subfamilies: NLRA, NLRB, NLRC, NLRP, and NLRX1. In this review, we briefly describe the structures and signaling pathways of NLRs, summarize the recent progress on NLR signaling in the occurrence and development of autoimmune diseases, as well as highlight numerous natural products and synthetic compounds targeting NLRs for the treatment of autoimmune diseases.

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Fig. 1: Protein structures of each NLR subfamily.
Fig. 2: Schematic representation of typical NLR signaling pathways.
Fig. 3: The effect of NLRs on autoimmune diseases.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC) (Grant Nos. 81903882 and 81871240), the National Science & Technology Major Project “New Drug Creation and Manufacturing Program” (Grant No. 2018ZX09711002-014-001), and the “Personalized Medicines—Molecular Signature-based Drug Discovery and Development”, Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDA12020369).

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Correspondence to Shi-jun He or Jian-ping Zuo.

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Chen, L., Cao, Sq., Lin, Zm. et al. NOD-like receptors in autoimmune diseases. Acta Pharmacol Sin (2021). https://doi.org/10.1038/s41401-020-00603-2

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Keywords

  • pattern recognition receptors
  • NOD-like receptors
  • autoimmune diseases
  • inflammasomes
  • inhibitors
  • botanicals

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