Ling Li and Zuoxiao Li* Pages 604 - 611 ( 8 )
Background: T follicular helper cells (Tfh) could help B cells induce humoral immunity response. Follicular regulatory T cells (Tfr) could inhibit the activity of Tfh cells effectively and the two kinds of cells are in a dynamic balance. Tofacitinib is a selective inhibitor of Jak1 and Jak3 and was approved for treating moderate to severe rheumatoid arthritis. It has proved that tofacitinib could effectively dampen the severity and progression of experimental autoimmune encephalomyelitis (EAE) by a decrease of Th1/Th17 cells and an increase in Tregs.So we speculate this drug may has effects on the Tfr/Tfh balance in EAE.
Method: A total of 50 female Wistar rats were randomly assigned into normal control group, EAE control group, and low-dose, median-dose, and high-dose to facitinib groups (10 for each). Rats were given subcutaneous injections of myelin basic protein from guinea pig spinal cord emulsified with complete Freund’s adjuvant (CFA) to induce the EAE model. The low-dose, median-dose, and high-dose tofacitinib groups were given tofacitinib 1, 2, and 4 mg/(kg·d), respectively, by gavage for 10 days from three days before. On the other hand, the normal and EAE control groups were given the same volume of saline. Incubation period, progressive stage, and neurological dysfunction score (NDS) at the peak of onset were recorded. Proportions of Tfh and Tfr cells and the ratio of Tfr/Tfh from the spleen were detected. Moreover, levels of CXCL13 and TGF-β1 in the cerebral homogenate were measured.
Results: In each tofacitinib group, the incubation period was extended, the progressive stage was shortened, and the NDS was reduced at the peak of onset. Proportion of Tfh cells and the level of CXCL13 significantly decreased, whereas the proportion of Tfr cells, the ratio of Tfr/Tfh, and the level of TGF-β1 significantly were increased compared with those in the EAE control group (P<0.01, P<0.05).
Conclusion: Tofacitinib may have a dampening effect on the severity and progression of EAE in a dose-dependent manner. This inhibiting effect of EAE may be associated with the down-regulation of the proportion of Tfh cells and expression of CXCL-13, and the up-regulation of the proportion of Tfr cells and expression of TGF-β1. Tofacitinib may modulate the balance of Tfr/Tfh and induce the balance to shift to Tfr.
Tofacitinib, experimental autoimmune encephalomyelitis, T follicular helper cells, follicular regulatory T cells, CXCL13, TGF-β1
Department of Neurology.Affiliated Hospital of Southwest Medical University,Luzhou Sichuan 646000, Department of Neurology.Affiliated Hospital of Southwest Medical University,Luzhou Sichuan 646000