2. Academic Validation
  3. Prophylactic administration of fingolimod (FTY720) ameliorated experimental autoimmune myasthenia gravis by reducing the number of dendritic cells, follicular T helper cells and antibody-secreting cells

Prophylactic administration of fingolimod (FTY720) ameliorated experimental autoimmune myasthenia gravis by reducing the number of dendritic cells, follicular T helper cells and antibody-secreting cells

  • Int Immunopharmacol. 2021 Jul;96:107511. doi: 10.1016/j.intimp.2021.107511.
Ying Liu 1,  Chun-Lin Yang 2,  Bing Yang 3,  Tong Du 4,  Xiao-Li Li 5,  Peng Zhang 6,  Meng-Ru Ge 7,  Ying Lian 8,  Heng Li 9,  Yu-Dong Liu 10,  Rui-Sheng Duan 11
Affiliations

Affiliations

  • 1 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China; Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, China. Electronic address: [email protected].
  • 2 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China. Electronic address: [email protected].
  • 3 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China. Electronic address: [email protected].
  • 4 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China. Electronic address: [email protected].
  • 5 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China. Electronic address: [email protected].
  • 6 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China. Electronic address: [email protected].
  • 7 Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, China. Electronic address: [email protected].
  • 8 Department of Health Management, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China. Electronic address: [email protected].
  • 9 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China. Electronic address: [email protected].
  • 10 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China. Electronic address: [email protected].
  • 11 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China; Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, China; Shandong Institute of Neuroimmunology, China. Electronic address: [email protected].
PMID: 33915521 DOI: 10.1016/j.intimp.2021.107511
Abstract

Fingolimod (FTY720), a sphingosine 1-phosphate (S1P) receptor antagonist, possesses potent immunomodulatory activity via lymphocyte homing. The effects of FTY720 have been widely studied in various T-cell-mediated autoimmune diseases, while the immunomodulatory effects on experimental autoimmune myasthenia gravis (EAMG), a typical disease model for antibody-mediated autoimmunity, remain elusive. In the present study, FTY720 was administered to EAMG rats as prophylaxis. The clinical scores were recorded every other day, and serum Antibodies at different time points were measured by enzyme-linked immunosorbent assay (ELISA). The immune cell subsets in the spleen, bone marrow, circulation, and thymus were determined by flow cytometry. The prophylactic administration alleviated EAMG symptoms by reducing the level of serum Antibodies IgG and its isotype IgG2B on days 30 and 46 post immunization, as well as IgG and Ig kappa antibody-secreting cells in the spleen and bone marrow. The mitigated humoral immune response can be attributed to the decreased dendritic cells, follicular T help cells (Tfh) and Tfh subsets (Tfh1, Tfh2, and Tfh17), and T helper cell subsets (Th1, Th2, and Th17) in the spleen. The promotion of lymphocyte homing and inhibition of thymocyte egress contribute to the effects of FTY720 on these effector T cell subsets. Overall, the prophylactic administration of FTY720 ameliorated EAMG partially by regulating humoral immune response，suggesting that FTY720 could be part of a pharmacological strategy for managing myasthenia gravis.

Keywords

Antibody-secreting cells; Dendritic cells; Experimental autoimmune myasthenia gravis; FTY720; Follicular helper T cells.

Figures
Products