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Direct reprogramming of fibroblasts into antigen-presenting dendritic cells
Fábio F Rosa1,2,3, Cristiana F Pires1,2,3, Ilia Kurochkin4
1Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, Sweden.
Science Immunology
|December 12, 2018
Summary
Researchers reprogrammed fibroblasts into dendritic cells (DCs) using specific transcription factors. These induced DCs (iDCs) can present antigens, offering potential for immunotherapy and understanding DC development.
Area of Science:
- Immunology
- Cell Biology
- Regenerative Medicine
Background:
- Transcription factor-mediated cell reprogramming is a key strategy in regenerative medicine.
- Generating specific cell types like dendritic cells (DCs) from somatic cells is crucial for therapeutic applications.
Purpose of the Study:
- To generate antigen-presenting dendritic cells (DCs) from mouse and human fibroblasts.
- To identify the minimal set of transcription factors required for this cellular reprogramming.
Main Methods:
- Screening of 18 transcription factors known to be expressed in DCs.
- Utilizing ectopic expression of identified transcription factors (PU.1, IRF8, BATF3) in fibroblasts.
- Characterization of induced DCs (iDCs) for transcriptional programs, cytokine secretion, antigen presentation, and T cell interaction.
Main Results:
- PU.1, IRF8, and BATF3 were sufficient to reprogram fibroblasts into induced DCs (iDCs).
- iDCs exhibited a conventional DC type 1-like transcriptional program with interferon-induced maturation features.
- iDCs secreted inflammatory cytokines and demonstrated antigen engulfment, processing, and presentation capabilities.
- Murine iDCs effectively cross-presented antigens to CD8+ T cells.
Conclusions:
- A novel reprogramming system efficiently generates iDCs from fibroblasts using three key transcription factors.
- This system advances the understanding of dendritic cell specification.
- The generated iDCs represent a promising platform for developing patient-specific DCs for immunotherapy.
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