Generation of Induced Pluripotent Stem Cells Derived Tolerogenic Dendritic Cells and Their Immunosuppressive Properties.

On this basis, we aimed to establish a protocol for generating tolDCs from iPSCs.

Methods

We modified an existing iPSC-to-DC induction protocol by adding minocycline and dexamethasone. Then, we assessed whether the resulting cells exhibited tolDC characteristics through comparison of iPSC-derived DCs (iPS-DCs) and iPSC-derived tolDCs (iPS-tolDCs). Results: We established a method for generating iPS-tolDCs from iPSCs.

Flow cytometric analysis revealed reduced expression of co-stimulatory molecules and the maturation marker in iPS-tolDCs compared with iPS-DCs. In co-culture experiments, CD4⁺CD45RA⁺ T cells isolated from PBMCs of healthy donors or patients with autoimmune diseases showed reduced proliferation when cultured with iPS-tolDCs compared with iPS-DCs. Gene expression profiles of iPS-tolDCs differed from those of iPS-DCs.

Conclusion: We developed a protocol for producing tolDCs from iPSCs and demonstrated their tolerogenic phenotype and immunosuppressive effects on T cells. These findings indicate that iPS-tolDCs are a promising candidate for cellular immunotherapy and warrant further investigation.