Advanced

Direct reprogramming of fibroblasts into antigen-presenting dendritic cells

Rosa, Fábio F. LU ; Pires, Cristiana F. LU ; Kurochkin, Ilia ; Ferreira, Alexandra G. LU ; Gomes, Andreia M. ; Palma, Luís G. ; Shaiv, Kritika ; Solanas, Laura ; Azenha, Cláudia and Papatsenko, Dmitri , et al. (2018) In Science Immunology 3(30).
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Immunology
volume
3
issue
30
article number
eaau4292
publisher
American Association for the Advancement of Science
external identifiers
  • scopus:85058594969
  • pmid:30530727
ISSN
2470-9468
DOI
10.1126/sciimmunol.aau4292
language
English
LU publication?
yes
id
e55030ac-0449-4fb3-b8ca-503cbf8c6911
date added to LUP
2019-01-03 13:23:57
date last changed
2020-07-08 04:37:30
@article{e55030ac-0449-4fb3-b8ca-503cbf8c6911,
  abstract     = {<p>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.</p>},
  author       = {Rosa, Fábio F. and Pires, Cristiana F. and Kurochkin, Ilia and Ferreira, Alexandra G. and Gomes, Andreia M. and Palma, Luís G. and Shaiv, Kritika and Solanas, Laura and Azenha, Cláudia and Papatsenko, Dmitri and Schulz, Oliver and E Sousa, Caetano Reis and Pereira, Carlos Filipe},
  issn         = {2470-9468},
  language     = {eng},
  month        = {12},
  number       = {30},
  publisher    = {American Association for the Advancement of Science},
  series       = {Science Immunology},
  title        = {Direct reprogramming of fibroblasts into antigen-presenting dendritic cells},
  url          = {http://dx.doi.org/10.1126/sciimmunol.aau4292},
  doi          = {10.1126/sciimmunol.aau4292},
  volume       = {3},
  year         = {2018},
}