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

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

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: yingxu825@126.com.
  • 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: scunn519@gmail.com.
  • 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: yt-wang@hotmail.com.
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z