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Mal-deficiency impairs the tolerogenicity of dendritic cell of patients with allergic rhinitis.

Authors
  • Shao, Jian-Bo1
  • Yang, Gui2
  • Zhang, Yuan-Yi3
  • Ma, Fei4
  • Luo, Xiang-Qian1
  • Mo, Li-Hua1
  • Liu, Zhi-Qiang2
  • Liao, Wen-Jing4
  • Qiu, Qian-Hui5
  • Li, Dong-Cai6
  • Yang, Li-Tao6
  • Zhang, Xiao-Wen7
  • Liu, Da-Bo8
  • Yang, Ping-Chang9
  • 1 Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, Shenzhen, China. , (China)
  • 2 Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China; Longgang ENT Hospital and Shenzhen ENT Institute, Shenzhen, China. , (China)
  • 3 Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China. , (China)
  • 4 Department of Otolaryngology, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. , (China)
  • 5 Department of Otolaryngology, Zhujiang Hospital of Southern Medical University, Guangzhou, China. , (China)
  • 6 Longgang ENT Hospital and Shenzhen ENT Institute, Shenzhen, China. , (China)
  • 7 Department of Otolaryngology, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. Electronic address: [email protected] , (China)
  • 8 Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, Shenzhen, China. Electronic address: [email protected] , (China)
  • 9 Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Cellular Immunology
Publisher
Elsevier
Publication Date
Oct 01, 2019
Volume
344
Pages
103930–103930
Identifiers
DOI: 10.1016/j.cellimm.2019.103930
PMID: 31196568
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The tolerogenic dendritic cell dysfunction is associated with the pathogenesis of immune diseases. Microbial stimulus is required in the maintenance of immune functions. This study aims to elucidate the role of Mal signal in the maintenance of DEC205+ DC (decDC) immune tolerogenic function. In this study, peripheral DCs were collected from allergic rhinitis (AR) patients and healthy control (HC) subjects to assess the functional status of decDCs. An AR murine model was developed to test the role of Mal signals in the maintenance of decDCs' functions. We observed that AR decDCs (decDCs obtained from AR patients) were incompetent in the induction of type 1 regulatory T cells (Tr1 cells). AR decDCs expressed less IL-10 than that in HC decDCs. IL-10 mRNA decayed spontaneously in AR decDCs. Tat-activating regulatory DNA-binding protein-43 (TDP43) protected IL-10 mRNA from decay. AR decDCs expressed lower levels of Mal than that in HC decDCs. Mal depletion resulted in IL-10 mRNA decay in HC decDCs. Reconstitution of Mal in AR decDCs restored the capacity of inducing Tr1 cells and attenuated experimental AR in mice. In conclusion, Mal plays a critical role in the maintenance of decDC's immune tolerogenic function. The absence or insufficient Mal signal impairs decDC's tolerogenic property. Reconstitution of Mal in AR decDCs can restore the immune tolerogenic capacity, which may have translational potential in the treatment of AR and other allergic diseases. Copyright © 2019 Elsevier Inc. All rights reserved.

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