2. Academic Validation
  3. A novel rare variant of CNPY3 from familial NMOSD impairs the TLR-mediated immune response

A novel rare variant of CNPY3 from familial NMOSD impairs the TLR-mediated immune response

  • J Neuroimmunol. 2023 Apr 15;377:578065. doi: 10.1016/j.jneuroim.2023.578065.
Yongxin Mo 1,  Shisi Wang 1,  Yanyu Chang 2,  Xiaobo Sun 1,  Zheng Liu 2,  Ping Sun 3,  Yan Xu 4,  Xiaofen Zhong 5,  Lisheng Peng 6
Affiliations

Affiliations

  • 1 Department of Neurology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
  • 2 Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
  • 3 Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
  • 4 Biotherapy Centre, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
  • 5 Biotherapy Centre, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China. Electronic address: [email protected].
  • 6 Department of Neurology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China. Electronic address: [email protected].
PMID: 36931208 DOI: 10.1016/j.jneuroim.2023.578065
Abstract

Toll-like receptors (TLRs) are a class of proteins that play essential roles in innate and adaptive immune responses. Recently, accumulating evidence has demonstrated that impairments in the TLR signalling pathway contribute to the development and progression of neuroimmune diseases, such as neuromyelitis optica spectrum disorder (NMOSD). However, the cellular and molecular mechanisms are still largely unknown. In this study, we report a novel variant, C52Y, of canopy FGF signalling regulator 3 (CNPY3) from patients with familial NMOSD and demonstrate that this variant shows a stronger interaction with GP96 and TLRs than with wild-type CNPY3. We find that C52Y has dominant negative effects on TLR4 surface expression. Importantly, the TLR4 surface expression level is decreased in RAW264.7 cells infected with the C52Y virus upon LPS stimulation. We further demonstrate that bone marrow-derived macrophages (BMDMs) from CNPY3C52Y/+ transgenic mice secrete less tumour necrosis factor (TNF) and interleukin (IL)-6 than BMDMs from wild-type mice upon stimulation with LPS. These data suggest that impairment of TLR trafficking may contribute to the development of neuroimmune disorders.

Keywords

Autoimmune; CNPY3; NMOSD; TLR.

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