Fig. 3. Schematic drawings of calcineurin inhibitor pathways in which a phosphatase dephosphorylates NFAT family members that then are transported into the nucleus and bind to the nuclear promotor of the IL-2 gene. Production of IL-2 will lead to full T-cell activation. Cyclosporine and tacrolimus show immunosuppression by directly interacting with calcineurin to inhibit its phosphatase action. While tacrolimus (FK506) binds to FK-binding protein (FKBP) to form an FK506-FKBP complex, cyclosporine (CsA) binds with cyclophilin to form a cyclophilin-cyclosporine complex. Both complexes directly inhibit calcineurin activity, leading to immunosuppression. Cyclosporine immunosuppression can be achieved by inhibition of MAPK. When MAPKs are activated by signal cascades, they translocate into the nucleus and phosphorylate activator protein 1 (AP-1), which is crucial for transcription of IL-2. Thus, blocking upstream of the MAPKKK cascade by cyclosporine leads to inhibition of MAPK activation and to immunosuppression. (NFAT: nuclear factor of activated T cell, IL-2: interleukin-2, JNK: Jun N-terminal kinase, MAPK: mitogen-activated protein kinase, MAPKK: MAPK kinase, MAPKKK: MAPK kinase kinase)

J Korean Assoc Oral Maxillofac Surg 2023;49:311~323
https://doi.org/10.5125/jkaoms.2023.49.6.311

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