PMID- 36931208
OWN - NLM
STAT- MEDLINE
DCOM- 20230810
LR  - 20230810
IS  - 1872-8421 (Electronic)
IS  - 0165-5728 (Linking)
VI  - 377
DP  - 2023 Apr 15
TI  - A novel rare variant of CNPY3 from familial NMOSD impairs the TLR-mediated immune 
      response.
PG  - 578065
LID - S0165-5728(23)00051-6 [pii]
LID - 10.1016/j.jneuroim.2023.578065 [doi]
AB  - 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 
      CNPY3(C52Y/+) 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.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Mo, Yongxin
AU  - Mo Y
AD  - Department of Neurology, Third Affiliated Hospital of Sun Yat-sen University, 
      Guangzhou 510630, China.
FAU - Wang, Shisi
AU  - Wang S
AD  - Department of Neurology, Third Affiliated Hospital of Sun Yat-sen University, 
      Guangzhou 510630, China.
FAU - Chang, Yanyu
AU  - Chang Y
AD  - Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
FAU - Sun, Xiaobo
AU  - Sun X
AD  - Department of Neurology, Third Affiliated Hospital of Sun Yat-sen University, 
      Guangzhou 510630, China.
FAU - Liu, Zheng
AU  - Liu Z
AD  - Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
FAU - Sun, Ping
AU  - Sun P
AD  - 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.
FAU - Xu, Yan
AU  - Xu Y
AD  - Biotherapy Centre, The Third Affiliated Hospital of Sun Yat-sen University, 
      Guangzhou 510630, China.
FAU - Zhong, Xiaofen
AU  - Zhong X
AD  - Biotherapy Centre, The Third Affiliated Hospital of Sun Yat-sen University, 
      Guangzhou 510630, China. Electronic address: zhongxf29@mail.sysu.edu.cn.
FAU - Peng, Lisheng
AU  - Peng L
AD  - Department of Neurology, Third Affiliated Hospital of Sun Yat-sen University, 
      Guangzhou 510630, China. Electronic address: penglsh5@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230308
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (CNPY3 protein, human)
RN  - 0 (CNPY3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Immunity
MH  - Interleukin-6
MH  - Lipopolysaccharides
MH  - Mice, Transgenic
MH  - *Neuromyelitis Optica/genetics/metabolism
MH  - Toll-Like Receptor 4/genetics
MH  - Toll-Like Receptors/metabolism
OTO - NOTNLM
OT  - Autoimmune
OT  - CNPY3
OT  - NMOSD
OT  - TLR
COIS- Declaration of Competing Interest The authors declare no conflicts of interest.
EDAT- 2023/03/18 06:00
MHDA- 2023/04/04 06:42
CRDT- 2023/03/17 19:10
PHST- 2022/12/29 00:00 [received]
PHST- 2023/02/09 00:00 [revised]
PHST- 2023/03/05 00:00 [accepted]
PHST- 2023/04/04 06:42 [medline]
PHST- 2023/03/18 06:00 [pubmed]
PHST- 2023/03/17 19:10 [entrez]
AID - S0165-5728(23)00051-6 [pii]
AID - 10.1016/j.jneuroim.2023.578065 [doi]
PST - ppublish
SO  - J Neuroimmunol. 2023 Apr 15;377:578065. doi: 10.1016/j.jneuroim.2023.578065. Epub 
      2023 Mar 8.