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Direct reprogramming of fibroblasts into antigen-presenting dendritic cells
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- Rosa, Fábio F. (author)
- Lund University,Lunds universitet,Cellulär omprogrammering i hematopoes och immunitet,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Cell Reprogramming in Hematopoiesis and Immunity,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,University of Coimbra
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- Pires, Cristiana F. (author)
- Lund University,Lunds universitet,Cellulär omprogrammering i hematopoes och immunitet,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Cell Reprogramming in Hematopoiesis and Immunity,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,University of Coimbra
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- Kurochkin, Ilia (author)
- Skolkovo Institute of Science and Technology
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- (creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2018
- 2018
- English.
- In: Science Immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 3:30
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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- Shaiv, Kritika
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