%0 Journal Article
%T VX-509 (Decernotinib)-modified tolerogenic dendritic cells alleviate experimental autoimmune neuritis by promoting Th17/Treg rebalance.
%A Li J
%A Chen S
%A Shi J
%A Yang F
%A Zhang G
%A Zhou Y
%A Kong Y
%A Luo X
%A Liu Y
%A Xu Y
%A Wang Y
%J Int Immunopharmacol
%V 138
%N 0
%D 2024 Sep 10
%M 38955025
%F 5.714
%R 10.1016/j.intimp.2024.112597
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.