Tuominjian decoction reduces the proportion of Tfh cells and B-cells in immune infertility male mice by regulating the seminal plasma levels of IL-1 and IL-6.

BACKGROUND

Male immunological infertility (MII), driven by anti-sperm antibody (AsAb), is a complex autoimmune disorder. The herbal formulation TuominJian (TMJ) has shown clinical efficacy against MII, but its immunomodulatory mechanisms involving Tfh cells, B cells, and cytokines remain unclear.

PURPOSE: This study aimed to elucidate the immunoregulatory effects and underlying mechanism of TMJ in MII mice.

METHODS

Active compounds in TMJ were identified using UPLC-Q/TOF-MS. An MII mouse model was established using sperm immunization. After verifying the model, testicular and epididymal tissue integrity, sperm parameters, and blood-testis barrier function were assessed via H&E staining, TEM, CASA, and western blotting. Serum AsAb, cytokines, and immune cell populations were analyzed by ELISA and flow cytometry.

RESULTS

Thirteen active compounds were identified in TMJ. TMJ treatment significantly reduced testicular cell apoptosis and decreased serum AsAb and proinflammatory cytokines (IL-1, IL-6). It also restored testicular and epididymal tissue architecture, improved sperm concentration and motility, and enhanced blood-testis barrier integrity by upregulating occludin. Furthermore, TMJ downregulated Tfh and B cell levels.

CONCLUSION

TMJ mitigates MII in mice by promoting structural recovery of reproductive tissues, reinforcing the blood-testis barrier, and modulating immune responses through suppression of Tfh cells, B cells, and proinflammatory cytokines. These findings highlight immunoregulation as a promising therapeutic strategy for MII.