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| Status |
Public on Sep 22, 2021 |
| Title |
Regulation of gene expression in splenic cDC1 isolated from WT vs XCR1-/- miceNK cells orchestrate cDC1 migration to potentiate antiviral protective CD8+ T cell responses |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The expression of the XCR1 chemokine receptor univocally identifies all type 1 conventional dendritic cells (cDC1) throughout the body. The gene encoding its ligand, XCL1, is expressed constitutively by innate lymphoid cells such as natural killer (NK) cells. The evolutionary conservation of XCR1, XCL1 in vertebrates suggests that they play a critical, yet uncharacterized, role in immune responses. Here we showed using mouse cytomegalovirus (MCMV) infection, that the XCL1/XCR1 axis promoted the intra-splenic repositioning of cDC1 towards IFN--producing NK cells forming superclusters around infected cells. There, cDC1 and NK cells engaged into physical interactions enhancing their respective production of IL-12 and IFN-. This feed-forward mechanism also led to NK cell production of GM-CSF, which upregulated CCR7 on cDC1, instructing them to migrate into the T cell area for the priming of CD8+ T cells. In conclusion, we identified a novel mechanism through which NK cells boost the relay between innate and adaptive immunities by regulating the spatiotemporal functions of cDC1.
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| Overall design |
C57BL/6J (WT) and XCR1-/- mice were infected with MCMV and their spleens were harvested 1.5 days (36h) after infection: CD11c+ cells were first enriched from each splenocyte suspension, then cDC1 were FACS-sorted, and used for pangenomic gene expression profiling by microarrays. Sorted cDC1 from spleen of uninfected WT and XCR1-/- mice were used as controls.
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| Contributor(s) |
Ghilas S, Ambrosini M, Cancel J, Massé M, Dalod M, Crozat K |
| Citation(s) |
34568787 |
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https://0-doi-org.brum.beds.ac.uk/10.1016/j.isci.2021.103059
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| Submission date |
Dec 20, 2019 |
| Last update date |
Sep 29, 2021 |
| Contact name |
Thien-Phong Vu Manh |
| Organization name |
CIML
|
| Street address |
163 avenue de Luminy
|
| City |
marseille |
| ZIP/Postal code |
13288 |
| Country |
France |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA596923 |
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