Direct reprogramming of fibroblasts into antigen-presenting dendritic cells

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Science Immunology  07 Dec 2018:
Vol. 3, Issue 30, eaau4292
DOI: 10.1126/sciimmunol.aau4292

“Induced” dendritic cells

In vitro systems that culture immune cells have contributed greatly in shaping our understanding of immune cell functions and in the development of immunotherapies. Taking a leaf from the regenerative medicine handbook, Rosa et al. found that ectopic expression of transcription factors PU.1, IRF8, and BATF3 reprogrammed mouse and human fibroblast cells to “induced” dendritic cells (iDCs). Human and murine iDCs were comparable to conventional type 1 DCs and had the ability to engulf and present antigens; murine iDCs could also cross-present antigens to CD8+ T cells. Their system could be useful in the clinic for generation of patient-specific DCs, and their studies open up the possibility of generating other DC subsets by reprogramming.


Ectopic expression of transcription factors has been used to reprogram differentiated somatic cells toward pluripotency or to directly reprogram them to other somatic cell lineages. This concept has been explored in the context of regenerative medicine. Here, we set out to generate dendritic cells (DCs) capable of presenting antigens from mouse and human fibroblasts. By screening combinations of 18 transcription factors that are expressed in DCs, we have identified PU.1, IRF8, and BATF3 transcription factors as being sufficient to reprogram both mouse and human fibroblasts to induced DCs (iDCs). iDCs acquire a conventional DC type 1–like transcriptional program, with features of interferon-induced maturation. iDCs secrete inflammatory cytokines and have the ability to engulf, process, and present antigens to T cells. Furthermore, we demonstrate that murine iDCs generated here were able to cross-present antigens to CD8+ T cells. Our reprogramming system should facilitate better understanding of DC specification programs and serve as a platform for the development of patient-specific DCs for immunotherapy.

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