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| Status |
Public on Aug 02, 2024 |
| Title |
Nuclear receptor Nur77 regulates immunomechanics of macrophages |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Macrophages exhibit remarkable plasticity in their morphology and mechanics, enabling them to adapt and execute essential inflammatory functions, such as navigating through inflamed tissue and pathogen engulfment. However, the precise regulatory mechanisms governing these dynamic changes in macrophage mechanics during inflammation remain poorly understood. Although the involvement of nuclear receptor Nur77 in macrophage inflammation has been extensively investigated, its potential correlation with cellular mechanics has not been investigated. In this study, we employ cytoskeletal imaging, single-cell acoustic force spectroscopy (AFS), migration and phagocytosis experiments, and RNA-sequencing analysis on bone marrow-derived macrophages (BMDMs) to compare wild-type (WT) and Nur77-deficient (Nur77-KO) cells. Our findings reveal that Nur77-KO BMDMs exhibit changes to their actin networks compared to WT BMDMs, which is associated with a stiffer and more rigid phenotype. Subsequent in-vitro experiments validated our observations, showcasing that Nur77 deficiency leads to enhanced migration, reduced adhesion, and increased phagocytic activity. The transcriptomics data confirmed altered mechanics-related pathways in Nur77-deficient macrophage that are accompanied by a robust pro-inflammatory phenotype. Utilizing previously obtained ChIP-data, we revealed that Nur77 directly targets differentially expressed genes associated with cellular mechanics. In conclusion, while Nur77 is recognized for its role in reducing inflammation of macrophages by inhibiting the expression of pro-inflammatory genes, our study identifies a novel regulatory mechanism where Nur77 governs macrophage inflammation through the modulation of expression of genes involved in cellular mechanics.
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| Overall design |
Comparison of gene expression in murine macrophages, derived from Nur77-deficient mice and wild-type mice, stimulated with 100 ng/ml LPS for 0, 4 and 18 hours. (n=4 per group for WT cells, n=3 per group for Nur77-deficient cells)
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| Contributor(s) |
Lith SC, Evers TM, Marton-Freire B, van Tiel CM, Mashaghi A, de Vries CJ |
| Citation(s) |
38763048 |
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| Submission date |
Jan 16, 2024 |
| Last update date |
Aug 02, 2024 |
| Contact name |
Claudia van Tiel |
| E-mail(s) |
c.m.vantiel@amsterdamumc.nl
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| Organization name |
Amsterdam UMC
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| Department |
Medical Biochemistry
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| Street address |
Meibergdreef 15
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| City |
Amsterdam |
| ZIP/Postal code |
1105AZ |
| Country |
Netherlands |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (21)
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| GSM8020481 |
BMDMs, Nur77-KO3_0h |
| GSM8020482 |
BMDMs, Nur77-KO3_4h |
| GSM8020483 |
BMDMs, Nur77-KO3_18h |
| GSM8020484 |
BMDMs, Nur77-KO4_0h |
| GSM8020485 |
BMDMs, Nur77-KO4_4h |
| GSM8020486 |
BMDMs, Nur77-KO4_18h |
| GSM8020487 |
BMDMs, WT1_0h |
| GSM8020488 |
BMDMs, WT1_4h |
| GSM8020489 |
BMDMs, WT1_18h |
| GSM8020490 |
BMDMs, WT2_0h |
| GSM8020491 |
BMDMs, WT2_4h |
| GSM8020492 |
BMDMs, WT2_18h |
| GSM8020493 |
BMDMs, WT3_0h |
| GSM8020494 |
BMDMs, WT3_4h |
| GSM8020495 |
BMDMs, WT3_18h |
| GSM8020496 |
BMDMs, WT4_0h |
| GSM8020497 |
BMDMs, WT4_4h |
| GSM8020498 |
BMDMs, WT4_18h |
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| Relations |
| BioProject |
PRJNA1065503 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE253423_raw_read_quant.table.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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