Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, remain foundational in preventing allograft rejection in solid organ transplantation. However, their long-term use is associated with complex immunomodulatory effects that extend beyond T-cell suppression, influencing immune architecture, lymphoid organ morphology, and systemic inflammatory profiles. This proposal outlines a systematic, review-based research framework aimed at synthesizing current evidence on the clinical manifestations and histopathological alterations induced by CNIs, with a specific focus on immune system remodeling and biomarker discovery. By integrating data from clinical outcomes, tissue-level changes, and molecular biomarkers, this study seeks to identify mechanistic pathways linking CNI exposure to immune dysregulation, infection susceptibility, and graft outcomes. The findings are expected to inform precision immunosuppression strategies and guide future translational research.

Solid organ transplantation represents a critical therapeutic intervention for end-stage organ failure, with immunosuppressive regimens forming the cornerstone of graft survival. Calcineurin inhibitors (CNIs), particularly cyclosporine and tacrolimus, exert their effects primarily through inhibition of calcineurin phosphatase activity, thereby suppressing nuclear factor of activated T-cells (NFAT) signaling and downstream cytokine transcription, including interleukin-2 (IL-2).

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