Concomitant inhibition of PPARγ and mTORC1 induces the differentiation of human monocytes into highly immunogenic dendritic cells.
Monocytes can differentiate into macrophages (Mo-Macs) or dendritic cells (Mo-DCs). The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the differentiation of monocytes into Mo-Macs, while the combination of GM-CSF/interleukin (IL)-4 is widely used to generate Mo-DCs for clinical applications and to study human DC biology. Here, we report that pharmacological inhibition of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in the presence of GM-CSF and the absence of IL-4 induces monocyte differentiation into Mo-DCs. Remarkably, we find that simultaneous inhibition of PPARγ and the nutrient sensor mammalian target of rapamycin complex 1 (mTORC1) induces the differentiation of Mo-DCs with stronger phenotypic stability, superior immunogenicity, and a transcriptional profile characterized by a strong type I interferon (IFN) signature, a lower expression of a large set of tolerogenic genes, and the differential expression of several transcription factors compared with GM-CSF/IL-4 Mo-DCs. Our findings uncover a pathway that tailors Mo-DC differentiation with potential implications in the fields of DC vaccination and cancer immunotherapy.
Pubmed ID: 36842088 RIS Download
Research resources used in this publication
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None foundAntibodies used in this publication
- Peroxidase-AffiniPure Goat Anti-Mouse IgG (H + L) (RRID:AB_10015289)
- beta Actin Loading Control Monoclonal Antibody (BA3R) (RRID:AB_2537660)
- Phospho-p70 S6 Kinase (Thr389) Antibody (RRID:AB_330944)
- FceR1 alpha Monoclonal Antibody (AER-37 (CRA1)), PE, eBioscience (RRID:AB_10804885)
- PE anti-human CD207 (Langerin) (RRID:AB_10897451)
- APC anti-human CD274 (B7-H1, PD-L1) (RRID:AB_2734441)
- Peroxidase-AffiniPure Goat Anti-Rabbit IgG (H+L) (min X Hu,Ms,Rat Sr Prot) (RRID:AB_2307391)
- Mouse Anti-CD4 Monoclonal Antibody, PerCP Conjugated, Clone L200 (RRID:AB_393791)
- Mouse Anti-CD8 Monoclonal Antibody, Phycoerythrin Conjugated, Clone RPA-T8 (RRID:AB_396581)
- Mouse Anti-IFN-gamma Monoclonal Antibody, Allophycocyanin Conjugated, Clone B27 (RRID:AB_398580)
- FastImmune Costim CD28/CD49d 0.3mL (RRID:AB_647457)
- Rat Anti-Tubulin Monoclonal Antibody, Unconjugated, Clone YOL1 / 34 (RRID:AB_305329)
- Alexa Fluor 488-AffiniPure Donkey Anti-Mouse IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Rb,Shp Sr Prot) (RRID:AB_2340846)
- HU CD1A PURE MAB 0.1MG HI149 (RRID:AB_396139)
- Anti-HLA-DR APC-Cy7 L243 (G46-6) RUO/GMP (RRID:AB_399974)
- Alexa Fluor 594-AffiniPure Donkey Anti-Rat IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rb,Shp Sr Prot) (RRID:AB_2340689)
- HLA-DR, DP, DQ (RRID:AB_10897011)
- CD80 (RRID:AB_10565975)
- Mouse Anti-CD16 Monoclonal Antibody, Phycoerythrin Conjugated, Clone B73.1 (RRID:AB_400331)
- Mouse Anti-CD1a Monoclonal Antibody, FITC Conjugated, Clone HI149 (RRID:AB_396140)
- Mouse Anti-CD1a Monoclonal Antibody, Allophycocyanin Conjugated, Clone HI149 (RRID:AB_398669)
- Mouse Anti-CD86 Monoclonal Antibody, Phycoerythrin Conjugated, Clone 2331 (FUN-1) (RRID:AB_396013)
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This is a list of tools and resources that we have found mentioned in this publication.
Peroxidase-AffiniPure Goat Anti-Mouse IgG (H + L) (antibody)
RRID:AB_10015289
This polyclonal targets IgG (H + L)
View all literature mentionsbeta Actin Loading Control Monoclonal Antibody (BA3R) (antibody)
RRID:AB_2537660
This monoclonal targets beta Actin Loading Control
View all literature mentionsPhospho-p70 S6 Kinase (Thr389) Antibody (antibody)
RRID:AB_330944
This polyclonal targets Phospho-p70 S6 Kinase (Thr389)
View all literature mentionsFceR1 alpha Monoclonal Antibody (AER-37 (CRA1)), PE, eBioscience (antibody)
RRID:AB_10804885
This monoclonal targets FceR1 alpha
View all literature mentionsPE anti-human CD207 (Langerin) (antibody)
RRID:AB_10897451
This monoclonal targets CD207
View all literature mentionsAPC anti-human CD274 (B7-H1, PD-L1) (antibody)
RRID:AB_2734441
This monoclonal targets CD274
View all literature mentionsPeroxidase-AffiniPure Goat Anti-Rabbit IgG (H+L) (min X Hu,Ms,Rat Sr Prot) (antibody)
RRID:AB_2307391
This polyclonal targets Rabbit IgG (H+L)
View all literature mentionsMouse Anti-CD4 Monoclonal Antibody, PerCP Conjugated, Clone L200 (antibody)
RRID:AB_393791
This monoclonal targets CD4
View all literature mentionsMouse Anti-CD8 Monoclonal Antibody, Phycoerythrin Conjugated, Clone RPA-T8 (antibody)
RRID:AB_396581
This monoclonal targets CD8
View all literature mentionsMouse Anti-IFN-gamma Monoclonal Antibody, Allophycocyanin Conjugated, Clone B27 (antibody)
RRID:AB_398580
This monoclonal targets IFN-γ
View all literature mentionsFastImmune Costim CD28/CD49d 0.3mL (antibody)
RRID:AB_647457
This monoclonal targets CD49d
View all literature mentionsRat Anti-Tubulin Monoclonal Antibody, Unconjugated, Clone YOL1 / 34 (antibody)
RRID:AB_305329
This monoclonal targets Tubulin
View all literature mentionsAlexa Fluor 488-AffiniPure Donkey Anti-Mouse IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Rb,Shp Sr Prot) (antibody)
RRID:AB_2340846
This unknown targets Mouse IgG (H+L)
View all literature mentionsHU CD1A PURE MAB 0.1MG HI149 (antibody)
RRID:AB_396139
This monoclonal targets CD1a
View all literature mentionsAnti-HLA-DR APC-Cy7 L243 (G46-6) RUO/GMP (antibody)
RRID:AB_399974
This monoclonal targets HLA-DR
View all literature mentionsAlexa Fluor 594-AffiniPure Donkey Anti-Rat IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rb,Shp Sr Prot) (antibody)
RRID:AB_2340689
This unknown targets Rat IgG (H+L)
View all literature mentionsHLA-DR, DP, DQ (antibody)
RRID:AB_10897011
This monoclonal targets HLA-DR, DP, DQ
View all literature mentionsMouse Anti-CD16 Monoclonal Antibody, Phycoerythrin Conjugated, Clone B73.1 (antibody)
RRID:AB_400331
This monoclonal targets CD16
View all literature mentionsMouse Anti-CD1a Monoclonal Antibody, FITC Conjugated, Clone HI149 (antibody)
RRID:AB_396140
This monoclonal targets CD1a
View all literature mentionsMouse Anti-CD1a Monoclonal Antibody, Allophycocyanin Conjugated, Clone HI149 (antibody)
RRID:AB_398669
This monoclonal targets CD1a
View all literature mentionsMouse Anti-CD86 Monoclonal Antibody, Phycoerythrin Conjugated, Clone 2331 (FUN-1) (antibody)
RRID:AB_396013
This monoclonal targets CD86 (B7-2)
View all literature mentions
