Immunological Regulation of DNA Methylation and its Implication in Allograft Rejection

Transplant rejection remains a major barrier to long-term graft survival and is driven by complex interactions between immune responses and molecular regulatory mechanisms. DNA methylation, a major epigenetic modification, plays an important role in regulating immune cell development, differentiation, maturation, and function. Aberrant DNA methylation can alter the expression of immune-related genes and influence the nature and intensity of immune responses. In transplantation, these changes may affect T cells, B cells, and innate immune cells involved in graft rejection. DNA methylation also contributes to the regulation of signaling pathways associated with immune activation, tolerance, and inflammatory responses. Changes in methylation patterns may therefore influence both the progression of rejection and the maintenance of graft function. This review summarizes current knowledge of DNA methylation in immune regulation and examines its implications for transplant rejection, with particular emphasis on thymic development, helper and cytotoxic T cells, regulatory T cells, B cells, innate immune cells, and signaling pathways. It also considers the potential relevance of DNA methylation as a biomarker and therapeutic target in transplantation. Understanding these epigenetic mechanisms may support the development of more precise approaches for assessing rejection risk, modulating immune responses, and improving long-term graft outcomes following solid organ transplantation.