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Aetiopathogenesis

 

TIM-3 regulates the NETs-mediated dendritic cell activation in myeloperoxidase-ANCA-associated vasculitis


1, 2, 3, 4, 5, 6, 7

 

  1. Department of Pathogen Biology and Department of Laboratory Medicine, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  2. Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  3. Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  4. Department of Laboratory Medicine, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  5. Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  6. Department of Laboratory Medicine, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  7. Department of Pathogen Biology and Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. haoyi@hust.edu.cn

CER13608
2021 Vol.39, N°2 ,Suppl.129
PI 0013, PF 0020
Aetiopathogenesis

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PMID: 33734972 [PubMed]

Received: 24/05/2020
Accepted : 07/09/2020
In Press: 09/03/2021
Published: 18/05/2021

Abstract

OBJECTIVES:
T cell immunoglobulin and mucin domain 3 (TIM-3) has been reported as an important regulatory molecule on T cells and plays a pivotal role in autoimmune diseases, but the impact on dendritic cells (DCs) is poorly explored. The formation of neutrophil extracellular traps (NETs) is considered as strongly implicated in the pathogenesis of autoimmune diseases, such as in myeloperoxidase-antineutrophil cytoplasmic autoantibody associated vasculitis (MPO-AAV). This study thus aimed to investigate the potential regulation roles of TIM-3 in the regulation of NETs-mediated DC activation in MPO-AAV.
METHODS:
Twenty untreated patients with MPO-AAV and 20 healthy controls were enrolled in this study. The expressions of TIM-3 and toll-like receptor 4 (TLR4) in peripheral blood dendritic cells were analysed by flow cytometry, and the release of NETs by neutrophils was evaluated by immunofluorescence. In animal experiments, we measured the DC activation markers after the stimulation of NETs. Furthermore, we detected the NETs-mediated DC activation after TIM-3 blockade.
RESULTS:
Here we found an increased spontaneous NET production in MPOAAV patients. We also revealed a markedly reduced expression of TIM-3 and an increased expression of TLR4 on DCs of active MPO-AAV patients. We found the NETs could induce the activation of DCs and promote Toll-like receptor 4 expression on DC surface. More interestingly, the blockade of TIM-3 could further enhance the NETs-mediated DC cytokine expression.
CONCLUSIONS:
Our results demonstrated DC surface TIM-3 plays an important role in maintaining the NETs mediated immune homeostasis in MPO-AAV, suggesting an important role in MPOAAV development.

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