Interleukin-10 causes interferon-γ-dependent emergency myelopoiesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA613303 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11348472.fastq.gz | Fastqsanger.gz | |||
| SRR11348473.fastq.gz | Fastqsanger.gz | |||
| SRR11348474.fastq.gz | Fastqsanger.gz | |||
| SRR11348475.fastq.gz | Fastqsanger.gz | |||
| SRR11348476.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Interleukin-10 causes interferon γ-dependent emergency myelopoiesis
| PRJNA721937 | ENA
Project description:In emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased myeloid cell production is observed, often mediated by the pro-inflammatory cytokine IFN-γ. IL-10 inhibits IFN-γ secretion, largely by its effects on macrophages and dendritic cells, but, paradoxically, its therapeutic administration to humans causes hematologic changes similar to those observed in EM. In this work we used different in vivo systems, including a humanized immune system mouse model, to show that IL-10 triggers EM, with a significant expansion of the myeloid progenitor compartment and production of myeloid cells. Hematopoietic progenitors display a prominent IFN-γ transcriptional signature, and we show that IFN-γ mediates IL-10-driven EM. We also found that IL-10, unexpectedly, induces IFN-γ production by all T cell subsets in vivo. Therefore, in addition to its established anti-inflammatory properties, IL-10 can induce IFN-γ production and EM, opening new perspectives for the design of IL-10-based immunotherapies.
2021-10-13 | GSE172060 | GEO
Project description:In emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased myeloid cell production is observed, often mediated by the pro-inflammatory cytokine IFN-γ. IL-10 inhibits IFN-γ secretion, largely by its effects on macrophages and dendritic cells, but, paradoxically, its therapeutic administration to humans causes hematologic changes similar to those observed in EM. In this work we used different in vivo systems, including a humanized immune system mouse model, to show that IL-10 triggers EM, with a significant expansion of the myeloid progenitor compartment and production of myeloid cells. Hematopoietic progenitors display a prominent IFN-γ transcriptional signature, and we show that IFN-γ mediates IL-10-driven EM. We also found that IL-10, unexpectedly, induces IFN-γ production by all T cell subsets in vivo. Therefore, in addition to its established anti-inflammatory properties, IL-10 can induce IFN-γ production and EM, opening new perspectives for the design of IL-10-based immunotherapies.
2021-10-13 | GSE147195 | GEO
Project description:Maternal IL-10 restricts fetal emergency myelopoiesis
| PRJNA1005679 | ENA
Project description:Systemic inflammation halts lymphopoiesis and prioritizes myeloid cell production. How blood cell production switches from homeostasis to emergency myelopoiesis is incompletely understood. Here we show that Lymphotoxin-b receptor (LTbR) signaling in combination with TNF and IL1 receptor signaling in mesenchymal stem cells (MSCs) downregulates Il7 expression to shutdown lymphopoiesis during systemic inflammation. LTbR signaling in MSCs also promoted CCL2 production to enable inflammatory monocyte egress from the bone marrow. Furthermore, pharmacological or genetic blocking of Il7 downregulation in MSCs impaired myeloid cell production and egress, which reduced survival against systemic bacterial and viral infections. Interestingly, lymphotoxin a1b2 delivered by B-lineage cells, and specifically by mature B cells, contributed to promote Il7 downregulation and reduce MSC lymphopoietic activity. Our studies revealed an unexpected role for LTbR signaling in MSCs and identified mature B cells as an important regulator of emergency myelopoiesis.
2023-01-20 | GSE218505 | GEO
Project description:We investigated how late fetal liver (FL) mouse hematopoieitic stem and progenitor cells (HSPC) respond to inflammation, with the hypothesis that deficits in engagement of emergency myelopoiesis (EM) pathways could limit neutrophil output and contribute to perinatal neutropenia, ultimately explaining the susceptibility of neonates to inflammation and infection. We show that fetal HSPCs are biased toward erythroid and lymphoid cell production at steady state and fail to mount classical EM responses in vivo. Despite being capable of responding to EM-inducing stimuli in vitro, we find that maternal factors like interleukin-10 (IL-10) restrict fetal HSPCs from activating EM pathways in utero. Accordingly, we find that loss of maternal IL-10 restores EM activation in fetal HSPCs but at a cost of premature parturition. These results reveal the evolutionary trade-off inherent in maternal anti-inflammatory responses that maintain pregnancy but render the fetus susceptible to infection.
2024-02-29 | GSE240914 | GEO
Project description:We investigated how late fetal liver (FL) mouse hematopoieitic stem and progenitor cells (HSPC) respond to inflammation, with the hypothesis that deficits in engagement of emergency myelopoiesis (EM) pathways could limit neutrophil output and contribute to perinatal neutropenia, ultimately explaining the susceptibility of neonates to inflammation and infection. We show that fetal HSPCs are biased toward erythroid and lymphoid cell production at steady state and fail to mount classical EM responses in vivo. Despite being capable of responding to EM-inducing stimuli in vitro, we find that maternal factors like interleukin-10 (IL-10) restrict fetal HSPCs from activating EM pathways in utero. Accordingly, we find that loss of maternal IL-10 restores EM activation in fetal HSPCs but at a cost of premature parturition. These results reveal the evolutionary trade-off inherent in maternal anti-inflammatory responses that maintain pregnancy but render the fetus susceptible to infection.
2024-02-29 | GSE240913 | GEO
Project description:We investigated how late fetal liver (FL) mouse hematopoieitic stem and progenitor cells (HSPC) respond to inflammation, with the hypothesis that deficits in engagement of emergency myelopoiesis (EM) pathways could limit neutrophil output and contribute to perinatal neutropenia, ultimately explaining the susceptibility of neonates to inflammation and infection. We show that fetal HSPCs are biased toward erythroid and lymphoid cell production at steady state and fail to mount classical EM responses in vivo. Despite being capable of responding to EM-inducing stimuli in vitro, we find that maternal factors like interleukin-10 (IL-10) restrict fetal HSPCs from activating EM pathways in utero. Accordingly, we find that loss of maternal IL-10 restores EM activation in fetal HSPCs but at a cost of premature parturition. These results reveal the evolutionary trade-off inherent in maternal anti-inflammatory responses that maintain pregnancy but render the fetus susceptible to infection.
2024-02-29 | GSE240912 | GEO
Project description:Maternal IL-10 restricts fetal emergency myelopoiesis [scATAC-seq]
| PRJNA1005686 | ENA
Project description:Maternal IL-10 restricts fetal emergency myelopoiesis [scRNA-seq]
| PRJNA1005683 | ENA