Direct reprogramming of fibroblasts into antigen-presenting dendritic cells

Fábio F. Rosa, Cristiana F. Pires, Ilia Kurochkin, Alexandra G. Ferreira, Andreia M. Gomes, Luís G. Palma, Kritika Shaiv, Laura Solanas, Cláudia Azenha, Dmitri Papatsenko, Oliver Schulz, Caetano Reis E. Sousa, Carlos Filipe Pereira

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbereaau4292
JournalScience Immunology
Volume3
Issue number30
DOIs
Publication statusPublished - 2018

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