Direct reprogramming of fibroblasts into antigen-presenting dendritic cells

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Direct reprogramming of fibroblasts into antigen-presenting dendritic cells. / Rosa, Fábio F.; Pires, Cristiana F.; Kurochkin, Ilia; Ferreira, Alexandra G.; Gomes, Andreia M.; Palma, Luís G.; Shaiv, Kritika; Solanas, Laura; Azenha, Cláudia; Papatsenko, Dmitri; Schulz, Oliver; E Sousa, Caetano Reis; Pereira, Carlos Filipe.

I: Science immunology, Vol. 3, Nr. 30, eaau4292, 07.12.2018.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Rosa, FF, Pires, CF, Kurochkin, I, Ferreira, AG, Gomes, AM, Palma, LG, Shaiv, K, Solanas, L, Azenha, C, Papatsenko, D, Schulz, O, E Sousa, CR & Pereira, CF 2018, 'Direct reprogramming of fibroblasts into antigen-presenting dendritic cells', Science immunology, vol. 3, nr. 30, eaau4292. https://doi.org/10.1126/sciimmunol.aau4292

APA

CBE

Rosa FF, Pires CF, Kurochkin I, Ferreira AG, Gomes AM, Palma LG, Shaiv K, Solanas L, Azenha C, Papatsenko D, Schulz O, E Sousa CR, Pereira CF. 2018. Direct reprogramming of fibroblasts into antigen-presenting dendritic cells. Science immunology. 3(30). https://doi.org/10.1126/sciimmunol.aau4292

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Rosa, Fábio F. ; Pires, Cristiana F. ; Kurochkin, Ilia ; Ferreira, Alexandra G. ; Gomes, Andreia M. ; Palma, Luís G. ; Shaiv, Kritika ; Solanas, Laura ; Azenha, Cláudia ; Papatsenko, Dmitri ; Schulz, Oliver ; E Sousa, Caetano Reis ; Pereira, Carlos Filipe. / Direct reprogramming of fibroblasts into antigen-presenting dendritic cells. I: Science immunology. 2018 ; Vol. 3, Nr. 30.

RIS

TY - JOUR

T1 - Direct reprogramming of fibroblasts into antigen-presenting dendritic cells

AU - Rosa, Fábio F.

AU - Pires, Cristiana F.

AU - Kurochkin, Ilia

AU - Ferreira, Alexandra G.

AU - Gomes, Andreia M.

AU - Palma, Luís G.

AU - Shaiv, Kritika

AU - Solanas, Laura

AU - Azenha, Cláudia

AU - Papatsenko, Dmitri

AU - Schulz, Oliver

AU - E Sousa, Caetano Reis

AU - Pereira, Carlos Filipe

PY - 2018/12/7

Y1 - 2018/12/7

N2 - 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.

AB - 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.

U2 - 10.1126/sciimmunol.aau4292

DO - 10.1126/sciimmunol.aau4292

M3 - Article

VL - 3

JO - Science immunology

T2 - Science immunology

JF - Science immunology

SN - 2470-9468

IS - 30

M1 - eaau4292

ER -