Regulatory dendritic cells and their usefulness in mitigating solid organ transplant rejection

Dendritic cells (DCs) are highly efficient antigen-presenting cells located throughout body tissues and surfaces. Initial studies described these cells as potent activators of naïve T lymphocytes; however, subsequent research has demonstrated that DCs can also regulate T cell activation, survival, and effector functions. DCs possessing T cell regulatory properties, known as regulatory DCs (regDCs), are phenotypically immature cells with modified functionality. In humans, regDCs are typically derived from blood monocytes and characterized by the surface marker expression profile CD11c^loCD-11b^hiCD14⁺HLA-DR⁺, low expression of major histocompatibility complex class I molecules, adhesion proteins, and costimulatory markers (e.g., CD40, CD80), and high expression of immune checkpoint and apoptosis-inducing ligands (e.g., PD-L1, Fas ligand). Additionally, these cells secrete abundant anti-inflammatory cytokines, including interleukin-10 and transforming growth factor-β. Preclinical studies using rodent and nonhuman primate models have demonstrated the efficacy of regDCs in mitigating allograft rejection. Likewise, clinical studies evaluating regDCs have confirmed their safety, efficacy, and feasibility for inducing antigen-specific immune tolerance and/or reducing solid organ transplant rejection. In this manuscript, we review the tolerogenic potential of regDCs, the mechanisms by which regDCs mediate immune tolerance, and the findings from preclinical and clinical studies assessing their use in mitigating solid organ transplant rejection.