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| Status |
Public on May 01, 2021 |
| Title |
Reduced frequencies and functional impairment of dendritic cell subsets and non-classical monocytes in MDS |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
In myelodysplastic syndromes (MDS) the immune system is involved in pathogenesis as well as in disease progression. Dendritic cells (DC) are key players of the immune system by serving as regulators of immune responses. Their function has been scarcely studied in MDS and most of the reported studies didn’t investigate naturally occurring DC subsets. Therefore, we here examined the frequency and function of DC subsets and slan+ non-classical monocytes in various MDS risk groups. Frequencies of DC as well as of slan+ monocytes were decreased in MDS bone marrow (BM) compared to normal bone marrow (NBM) samples. Transcriptional profiling revealed down-regulation of transcripts related to pro-inflammatory pathways in MDS-derived cells as compared to NBM. Additionally, their capacity to induce T cell proliferation was impaired. Multidimensional mass cytometry showed that whereas healthy donor-derived slan+ monocytes supported Th1/Th17/Treg differentiation/expansion their MDS-derived counterparts also mediated substantial Th2 expansion. Our findings point to a role for an impaired ability of DC subsets to adequately respond to cellular stress and DNA damage in the immune escape and progression of MDS. As such, it paves the way toward potential novel immunotherapeutic interventions.
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| Overall design |
Genome-wide transcriptional analysis of cDC2 and slan+ monocytes from healthy donor- and MDS-derived bone marrow.
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| Contributor(s) |
van Leeuwen-Kerkhoff N, Westers TM, Poddighe PJ, Povoleri GA, Timms JA, Kordasti S, de Gruijl TD, van de Loosdrecht AA |
| Citation(s) |
33567812 |
| Submission date |
Nov 09, 2020 |
| Last update date |
Mar 31, 2022 |
| Contact name |
Nathalie van Leeuwen-Kerkhoff |
| E-mail(s) |
n.kerkhoff@amsterdamumc.nl
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| Organization name |
Amsterdam UMC
|
| Lab |
Nathalie van Leeuwen-Kerkhoff
|
| Street address |
De Boelelaan 1117
|
| City |
Utrecht |
| State/province |
The Netherlands |
| ZIP/Postal code |
3581 JT |
| Country |
Netherlands |
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| Platforms (1) |
| GPL23126 |
[Clariom_D_Human] Affymetrix Human Clariom D Assay [transcript (gene) version] |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA675462 |
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