Tacrolimus Modulates Peripheral Blood
NK
Cell Subsets and
IL
‐17/
IL
‐10 Ratio in Women With Recu
Marzieh Zamaniyan, Sepideh Peivandi, Imaneh Ahmadi, Fatemeh Ghasemzadeh, Mohammad Malekan, Behshad Bahri, Maryam Lotfi, Hossein Asgarian‐Omran, Saeid Taghiloo ABSTRACT
Purpose
Recurrent implantation failure (RIF) is linked to immune dysregulation. Although tacrolimus has shown clinical benefits in RIF, its immunological mechanisms remain unclear. We assessed its effects on peripheral blood NK cell subsets and cytokine profiles.
Methods
Thirty women with RIF and 30 fertile controls were enrolled. Patients received oral tacrolimus (3 mg/day) before embryo transfer until pregnancy testing. NK cell subsets and IL‐17/IL‐10 expression were assessed by flow cytometry and real‐time PCR before and after treatment.
Results
At baseline, RIF patients showed higher NK cell‐associated subsets and increased IL‐17/IL‐10 ratio compared with controls (CD16 + : p = 0.019; CD56 + : p < 0.0001; CD16 + CD56 + : p < 0.0001; IL‐17/IL‐10 ratio: p < 0.0001). Following tacrolimus, CD16 + ( p = 0.011), CD56 + ( p = 0.001), and CD16 + CD56 + ( p = 0.001) NK cells, as well as IL‐17 levels ( p < 0.0001) and the IL‐17/IL‐10 ratio ( p = 0.0036), were significantly reduced, whereas IL‐10 expression remained unchanged ( p = 0.406). Greater reductions in the IL‐17/IL‐10 ratio were associated with clinical pregnancy ( p = 0.048), suggesting predictive value for implantation success.
Conclusions
Tacrolimus modulated immune pathways by reducing pro‐inflammatory NK subsets and shifting the IL‐17/IL‐10 balance toward tolerance, supporting its potential as targeted immunotherapy in selected patients.