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| Regulation of Th17/Treg Balance by BAFF in a Mouse Model of Immune Thrombocytopenia |
| LI Wei, MA Xihu, LIU Xiao, et al |
| The Fourth Affiliated Hospital of Xinjiang Medical University, Xinjiang Urumqi 830001, China |
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Abstract Objective: To explore the regulatory role of B-cell activating factor (BAFF) on the balance of helper T cell 17 (Th17) and regulatory T cell (Treg) in vivo in a mouse model of immune thrombocytopenia (ITP).Methods: Guinea pig anti-mouse platelet serum (GP-APS) was prepared, and 150 adult male BALB/c mice (7-8 weeks old) were randomly divided into 5 groups (n=30 per group): control (blank control), ITP (induced by GP-APS), ITP+rhBAFF (ITP mice treated with intravenous injection of recombinant human BAFF protein at 50μg/kg/50μL), ITP+rhBAFF+DAPT (combined with Notch1 inhibitor DAPT), and ITP+rhBAFF+PGD (combined with PI3K/Akt inhibitor Polygalacin D). DAPT was injected at 100μg/kg, and PGD at 25 μg/kg, both with a total volume of 50μL and administered once daily. Peripheral blood (1mL) was collected from mice after 1 week for serum and mononuclear cell isolation. Immunofluorescence staining was used to detect BAFF and Notch1 localization in mononuclear cells. Platelet counts in peripheral blood were determined. Enzyme-linked immunosorbent assay (ELISA) was performed to measure BAFF levels in mouse serum. Western blotting was conducted to assess protein expression of PI3K, AKT, Notch1, p-Akt(Thr308), and p-Akt(Ser473) in mononuclear cells. Flow cytometry was used to analyze changes in Th17/Treg ratio in mononuclear cells.Results: BAFF and Notch1 were co-localized on the cell membrane of mononuclear cells in peripheral blood of ITP mice. Compared with the control group, ITP group showed increased expression of BAFF, Notch1, p-Akt(Thr308), p-Akt(Ser473), increased Th17 proportion, decreased platelet count, and decreased Treg proportion (P<0.05). Compared with the ITP group, ITP+rhBAFF group exhibited increased BAFF, Notch1, p-Akt(Thr308), p-Akt(Ser473) expression, increased Th17 proportion, decreased platelet count, and decreased Treg proportion (P<0.05). Compared with the ITP+rhBAFF group, both ITP+rhBAFF+DAPT and ITP+rhBAFF+PGD groups showed decreased BAFF, Notch1, p-Akt(Thr308), p-Akt(Ser473) expression, increased platelet count, increased Treg proportion, and decreased Th17 proportion (P<0.05).Conclusion: BAFF promotes an increase in Th17 proportion and decrease in Treg proportion in a mouse model of immune thrombocytopenia by activating the Notch1/PI3K/Akt signaling pathway.
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2024, Vol. 30 
