VX-509 (Decernotinib)-modified tolerogenic dendritic cells alleviate experimental autoimmune neuritis by promoting Th17/Treg rebalance

  • Int Immunopharmacol. 2024 Sep 10:138:112597. doi: 10.1016/j.intimp.2024.112597.
Juan Li  1 ,  Shan Chen  1 ,  Jiao Shi  1 ,  Fan Yang  1 ,  Gan Zhang  1 ,  Yan Zhou  2 ,  Yuhang Kong  1 ,  Xingyan Luo  1 ,  Yang Liu  3 ,  Ying Xu  4 ,  Yantang Wang  5
Affiliations
  • 1. Clinical Laboratory, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu 610500, Sichuan, China; Department of Pharmacology, School of Pharmacy, Chengdu Medical College, Chengdu, 610500, Sichuan, China.
  • 2. Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
  • 3. Clinical Laboratory, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu 610500, Sichuan, China; Department of Pharmacology, School of Pharmacy, Chengdu Medical College, Chengdu, 610500, Sichuan, China. Electronic address: [email protected].
  • 4. Clinical Laboratory, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu 610500, Sichuan, China; Department of Pharmacology, School of Pharmacy, Chengdu Medical College, Chengdu, 610500, Sichuan, China. Electronic address: [email protected].
  • 5. Clinical Laboratory, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu 610500, Sichuan, China; Department of Pharmacology, School of Pharmacy, Chengdu Medical College, Chengdu, 610500, Sichuan, China. Electronic address: [email protected].
PMID: 38955025 DOI: 10.1016/j.intimp.2024.112597
Abstract

Background: Guillain-Barré syndrome (GBS) is an auto-inflammatory peripheral nerve disease. Dendritic cell-mediated T cell polarization is of pivotal importance in demyelinating lesions of peripheral nerves and nerve roots. However, the regulatory function of VX-509 (Decernotinib)-modified tolerogenic dendritic cells (VX-509-tolDCs) during immune remodeling following GBS remains unclear. Here, we used experimental autoimmune neuritis (EAN) as a model to investigate these aspects of GBS.

Methods: DCs were treated with varying concentrations of VX-509 (0.25, 1, and 4 μM) or served as a control using 10-8 M 1,25-(OH)2D3. Flow cytometry was employed to assess the Apoptosis, phenotype, and capacity to induce T cell responses of the treated DCs. In the in vivo experiments, EAN mice received administration of VX-509-tolDCs or 1,25-(OH)2D3-tolDCs via the tail vein at a dose of 1x106 cells/mouse on days 5, 9, 13, and 17.

Results: VX-509 inhibited the maturation of DCs and promoted the development of tolDCs. The function of antigen-specific CD4 + T cells ex vivo was influenced by VX-509-tolDCs. Furthermore, the adoptive transfer of VX-509-tolDCs effectively alleviated inflammatory demyelinating lesions in EAN by promoting Th17/Treg (T helper 17 and regulatory T cells) rebalance.

Conclusion: The adoptive transfer of VX-509-tolDCs alleviated inflammatory demyelinating lesions in a mouse model of GBS, known as the EAN mouse, by partially restoring the balance between Treg and Th17 cells.

Keywords
Experimental autoimmune neuritis; Guillain-Barré syndrome; Th17 cells; Tolerogenic dendritic cells; Treg cells; VX-509.
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