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| Status |
Public on May 26, 2021 |
| Title |
Lysosome-dependent LXR and PPARdelta Activation upon Efferocytosis in Human Macrophages |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Efferocytosis is critical for tissue homeostasis, as its deregulation is associated with several autoimmune pathologies. While engulfing apoptotic cells, phagocytes activate transcription factors, such as peroxisome proliferator-activated receptors (PPAR) or liver X receptors (LXR) that orchestrate metabolic, phagocytic, and inflammatory responses towards the ingested material. Coordination of these transcription factors in efferocytotic human macrophages (MF) is not fully understood. In this study, we evaluated the transcriptional profile of MF following the uptake of apoptotic Jurkat T cells using RNA-seq analysis. Results indicated upregulation of PPAR and LXR pathways but downregulation of sterol regulatory element-binding proteins (SREBP) target genes. Pharmacological inhibition and RNA interference pointed to LXR and PPARdelta as relevant transcriptional regulators, while PPARdelta did not substantially contribute to gene regulation. Mechanistically, lysosomal digestion and lysosomal acid lipase (LIPA) were required for PPAR and LXR activation, while PPARdelta activation also demanded an active lysosomal phospholipase A2 (PLA2G15). Pharmacological interference with LXR signaling attenuated ABCA1-dependent cholesterol efflux from efferocytotic MF, but suppression of inflammatory responses following efferocytosis occurred independently of LXR and PPARdelta. These data provide mechanistic details on LXR and PPARdelta activation in efferocytotic human MF.
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| Overall design |
mRNA-seq of human primary macrophages co-cultured with apoptotic Jurkat T cells at a 1:3 ratio for 3 hours, followed by AC removal and subsequent incubation for 3 hours. (n=6)
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| Contributor(s) |
Mota AC, Namgaladze D |
| Citation(s) |
34025647 |
| |
| Submission date |
Mar 18, 2021 |
| Last update date |
May 26, 2021 |
| Contact name |
Tobias Schmid |
| Organization name |
Goethe-University Frankfurt
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| Department |
Institute of Biochemistry I
|
| Street address |
Theodor-Stern-Kai 7
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| City |
Frankfurt |
| ZIP/Postal code |
60590 |
| Country |
Germany |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA715460 |
| SRA |
SRP311217 |
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