Tacrolimus maintains the balance of NETs by inducing DNA methylation of neutrophils to reduce immune rejection

Abstract

Abstract Background The immune rejection is a major concern in organ transplantation and can cause damage to the transplanted organ and ultimately lead to its failure. To prevent or treat immune rejection, transplant recipients are typically given immunosuppressive drugs to suppress their immune system. Tacrolimus is an immunosuppressive drug that is commonly used to prevent or treat immune rejection in organ transplantation. NETs formation and function in innate immunity and inflammation. NETs play an antimicrobial role, but excessive NETs are harmful and can cause inflammation and tissue damage. Methods To clarify the mechanism by which tacrolimus suppresses immune rejection, we used HL-60 cells, induced them to become neutrophils with DMSO, and then induced NETs with PMA. By comparing the changes before and after treatment with tacrolimus, we elucidated whether tacrolimus can change NETs formation. Results In this experiment, we found that tacrolimus can increase DNA methylation, which may be an important reason for the reduction of NETs by tacrolimus, as DNA methylation can stabilize DNA structure, making DNA better able to maintain its own structure. More research is needed to fully understand the relationship between DNA methylation, NETs formation, and immune rejection in organ transplantation, and to determine the potential therapeutic use of drugs that modulate DNA methylation or NETs. Conclusions In conclusion, we have found for the first time that tacrolimus can inhibit the production of NETs by enhancing the DNA methylation of cells, thereby exerting a better immunosuppressive effect. This may be a new mechanism for tacrolimus. We use this mechanism to provide new guidance for clinical research and immunosuppression and rehabilitation in the process of organ inhibition.