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| Status |
Public on Jun 02, 2020 |
| Title |
IL-12 From Endogenous cDC1, and Not Vaccine DC, Is Required for Th1 Induction |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In this study, we generated a chimeric situation by injection of different gene-modified BM-DCs into different strains of gene-modified recipient mice. This allowed us to identify the separate functional contributions of injected versus endogenous DCs for Th1 polarization. We identified the cellular source of IL-12p70 production after subcutaneous BM-DC vaccination as endogenous migratory XCR1+ bystander DCs in the skin draining lymph nodes. DC-DC and DCT cell interaction studies revealed a time course of Th0 priming by injected BM-DCs, followed by interactions of BM-DC with the IL-12+ XCR1+ bystander DCs, and finally IL-12+ XCR1+ bystander DC interactions for Th1 induction. Transcriptional profiling of the bystander DCs underscores their Th1 polarization potential. Together, this study shows that DC-vaccination requires the bystander activation of endogenous DCs for Th1 priming. Our data also challenge the general concept of Th1 priming by a single DC providing all signals 1, 2 and 3 to T cells for Th1 polarization.
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| Overall design |
To study the transcriptional changes occurring in the endogenous migratory bystander DCs, we sorted the migratory MHC II high CD11c+ lymph node DC subsets before (naive mice) and 48h after BM-DC injection (bystander activation). Thereby we could compare migratory XCR1+ CD11b- dDCs (cDC1s), CD11b+ XCR1- dDCs (cDC2s), and CD11b- XCR1- DCs (DN) at steady-state and 48h after LPS.BM-DC injection. Also, the appearance of CD11b+ CD64+ Ly6Clow inflammation-induced MoDCs was identified and these cells were also sorted at 48h.
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| Contributor(s) |
Ashour D, Arampatzi P, Förstner KU, Kaisho T, Beilhack A, Erhard F, Lutz MB |
| Citation(s) |
32434994 |
| |
| Submission date |
Jan 04, 2019 |
| Last update date |
Jun 03, 2020 |
| Contact name |
Tom Gräfenhan |
| E-mail(s) |
ht-seq.sysmed@uni-wuerzburg.de
|
| Phone |
+49 - 931 - 31 - 80814
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| Organization name |
University of Wuerzburg
|
| Department |
Core Unit SysMed
|
| Lab |
Raum D15.02.045
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| Street address |
Josef-Schneider-Str. 2, Bau D15
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| City |
Würzburg |
| ZIP/Postal code |
97080 |
| Country |
Germany |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA513047 |
| SRA |
SRP175307 |
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