Two distinct interstitial macrophage populations coexist across tissues in unique subtissular niches [FACs sorted]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE125667 | GEO | 2019/01/26
REPOSITORIES: GEO
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Project description:Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation and in multiple pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within tissue parenchyma remain poorly defined. Here, we studied IMs from murine lung, fat, heart and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localisation. Using a mouse model of inducible macrophage depletion (SLCO2B1-DTR), we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs exist across tissues and exhibit conserved niche-dependent functional programming.
2019-01-26 | GSE125676 | GEO
Project description:Pulmonary resident macrophages consist of alveolar macrophages (AMs) and interstitial macrophages (IMs). While much is known about the role of AMs, the function of IMs, which are conserved across multiple organs and species, remains unclear. Using single-cell RNA sequencing (scRNA-seq) after inducing acute lung injury, we identified at least six distinct subtypes of pulmonary IMs, based on the chemokines they express. These subtypes are: IMck1 (Ccl2, Ccl7, Ccl12, a few Cxcl14); IMck2-4 (Ccl3, Ccl4, Ccl5, Cxcl2, Cxcl3); IMck5-7 (Ccl6, Ccl8, Ccl9); IMck8 (Cxcl9, Cxcl10); IMck9 (Cxcl13); and IMck10 (Ccl24). Based on the selective chemokine expression profiles observed, we hypothesized that pulmonary IMs play a critical role in recruiting leukocytes and forming inducible bronchus-associated lymphoid tissue (iBALT) in the lung. First, we examined multiple Cre-expressing mice (Lyve1, Nes, Pdpn, and Pf4) for IM specificity by crossing them with Rosa26EYFP. Only the Pf4Cre mice selectively induced EYFP expression in CD206hiCD64hi IMs, where no other immune cell in the lung expressed EYFP. We then created a CD206hiCD64hi IM-depleting mouse by crossing Pf4Cre with Rosa26DTR and CX3CR1_001DTR. In a bacterial infection and allergic airway disease, depletion of CD206hiCD64hi IMs resulted in diminished leukocyte recruitment and iBALT formation. Overall, our study highlights the increased granularity in IM populations and demonstrates a division of labor for cellular recruitment and iBALT formation in the lung. Furthermore, the study suggests that the specific combination of chemokines expressed by IMs are tightly regulated, like Th cytokine-producing cells.
2023-03-03 | GSE225667 | GEO
Project description:Pulmonary resident macrophages consist of alveolar macrophages (AMs) and interstitial macrophages (IMs). While much is known about the role of AMs, the function of IMs, which are conserved across multiple organs and species, remains unclear. Using single-cell RNA sequencing (scRNA-seq) after inducing acute lung injury, we identified at least six distinct subtypes of pulmonary IMs, based on the chemokines they express. These subtypes are: IMck1 (Ccl2, Ccl7, Ccl12, a few Cxcl14); IMck2-4 (Ccl3, Ccl4, Ccl5, Cxcl2, Cxcl3); IMck5-7 (Ccl6, Ccl8, Ccl9); IMck8 (Cxcl9, Cxcl10); IMck9 (Cxcl13); and IMck10 (Ccl24). Based on the selective chemokine expression profiles observed, we hypothesized that pulmonary IMs play a critical role in recruiting leukocytes and forming inducible bronchus-associated lymphoid tissue (iBALT) in the lung. First, we examined multiple Cre-expressing mice (Lyve1, Nes, Pdpn, and Pf4) for IM specificity by crossing them with Rosa26EYFP. Only the Pf4Cre mice selectively induced EYFP expression in CD206hiCD64hi IMs, where no other immune cell in the lung expressed EYFP. We then created a CD206hiCD64hi IM-depleting mouse by crossing Pf4Cre with Rosa26DTR and CX3CR1DTR. In a bacterial infection and allergic airway disease, depletion of CD206hiCD64hi IMs resulted in diminished leukocyte recruitment and iBALT formation. Overall, our study highlights the increased granularity in IM populations and demonstrates a division of labor for cellular recruitment and iBALT formation in the lung. Furthermore, the study suggests that the specific combination of chemokines expressed by IMs are tightly regulated, like Th cytokine-producing cells.
2023-03-03 | GSE225666 | GEO
Project description:Pulmonary resident macrophages consist of alveolar macrophages (AMs) and interstitial macrophages (IMs). While much is known about the role of AMs, the function of IMs, which are conserved across multiple organs and species, remains unclear. Using single-cell RNA sequencing (scRNA-seq) after inducing acute lung injury, we identified at least six distinct subtypes of pulmonary IMs, based on the chemokines they express. These subtypes are: IMck1 (Ccl2, Ccl7, Ccl12, a few Cxcl14); IMck2-4 (Ccl3, Ccl4, Ccl5, Cxcl2, Cxcl3); IMck5-7 (Ccl6, Ccl8, Ccl9); IMck8 (Cxcl9, Cxcl10); IMck9 (Cxcl13); and IMck10 (Ccl24). Based on the selective chemokine expression profiles observed, we hypothesized that pulmonary IMs play a critical role in recruiting leukocytes and forming inducible bronchus-associated lymphoid tissue (iBALT) in the lung. First, we examined multiple Cre-expressing mice (Lyve1, Nes, Pdpn, and Pf4) for IM specificity by crossing them with Rosa26EYFP. Only the Pf4Cre mice selectively induced EYFP expression in CD206hiCD64hi IMs, where no other immune cell in the lung expressed EYFP. We then created a CD206hiCD64hi IM-depleting mouse by crossing Pf4Cre with Rosa26DTR and CX3CR1DTR. In a bacterial infection and allergic airway disease, depletion of CD206hiCD64hi IMs resulted in diminished leukocyte recruitment and iBALT formation. Overall, our study highlights the increased granularity in IM populations and demonstrates a division of labor for cellular recruitment and iBALT formation in the lung. Furthermore, the study suggests that the specific combination of chemokines expressed by IMs are tightly regulated, like Th cytokine-producing cells.
2023-03-03 | GSE225665 | GEO
Project description:Pulmonary resident macrophages consist of alveolar macrophages (AMs) and interstitial macrophages (IMs). While much is known about the role of AMs, the function of IMs, which are conserved across multiple organs and species, remains unclear. Using single-cell RNA sequencing (scRNA-seq) after inducing acute lung injury, we identified at least six distinct subtypes of pulmonary IMs, based on the chemokines they express. These subtypes are: IMck1 (Ccl2, Ccl7, Ccl12, a few Cxcl14); IMck2-4 (Ccl3, Ccl4, Ccl5, Cxcl2, Cxcl3); IMck5-7 (Ccl6, Ccl8, Ccl9); IMck8 (Cxcl9, Cxcl10); IMck9 (Cxcl13); and IMck10 (Ccl24). Based on the selective chemokine expression profiles observed, we hypothesized that pulmonary IMs play a critical role in recruiting leukocytes and forming inducible bronchus-associated lymphoid tissue (iBALT) in the lung. First, we examined multiple Cre-expressing mice (Lyve1, Nes, Pdpn, and Pf4) for IM specificity by crossing them with Rosa26EYFP. Only the Pf4Cre mice selectively induced EYFP expression in CD206hiCD64hi IMs, where no other immune cell in the lung expressed EYFP. We then created a CD206hiCD64hi IM-depleting mouse by crossing Pf4Cre with Rosa26DTR and CX3CR1DTR. In a bacterial infection and allergic airway disease, depletion of CD206hiCD64hi IMs resulted in diminished leukocyte recruitment and iBALT formation. Overall, our study highlights the increased granularity in IM populations and demonstrates a division of labor for cellular recruitment and iBALT formation in the lung. Furthermore, the study suggests that the specific combination of chemokines expressed by IMs are tightly regulated, like Th cytokine-producing cells.
2023-03-03 | GSE225664 | GEO
Project description:Pulmonary resident macrophages consist of alveolar macrophages (AMs) and interstitial macrophages (IMs). While much is known about the role of AMs, the function of IMs, which are conserved across multiple organs and species, remains unclear. Using single-cell RNA sequencing (scRNA-seq) after inducing acute lung injury, we identified at least six distinct subtypes of pulmonary IMs, based on the chemokines they express. These subtypes are: IMck1 (Ccl2, Ccl7, Ccl12, a few Cxcl14); IMck2-4 (Ccl3, Ccl4, Ccl5, Cxcl2, Cxcl3); IMck5-7 (Ccl6, Ccl8, Ccl9); IMck8 (Cxcl9, Cxcl10); IMck9 (Cxcl13); and IMck10 (Ccl24). Based on the selective chemokine expression profiles observed, we hypothesized that pulmonary IMs play a critical role in recruiting leukocytes and forming inducible bronchus-associated lymphoid tissue (iBALT) in the lung. First, we examined multiple Cre-expressing mice (Lyve1, Nes, Pdpn, and Pf4) for IM specificity by crossing them with Rosa26EYFP. Only the Pf4Cre mice selectively induced EYFP expression in CD206hiCD64hi IMs, where no other immune cell in the lung expressed EYFP. We then created a CD206hiCD64hi IM-depleting mouse by crossing Pf4Cre with Rosa26DTR and CX3CR1DTR. In a bacterial infection and allergic airway disease, depletion of CD206hiCD64hi IMs resulted in diminished leukocyte recruitment and iBALT formation. Overall, our study highlights the increased granularity in IM populations and demonstrates a division of labor for cellular recruitment and iBALT formation in the lung. Furthermore, the study suggests that the specific combination of chemokines expressed by IMs are tightly regulated, like Th cytokine-producing cells.
2023-03-03 | GSE225663 | GEO
Project description:Pulmonary resident macrophages consist of alveolar macrophages (AMs) and interstitial macrophages (IMs). While much is known about the role of AMs, the function of IMs, which are conserved across multiple organs and species, remains unclear. Using single-cell RNA sequencing (scRNA-seq) after inducing acute lung injury, we identified at least six distinct subtypes of pulmonary IMs, based on the chemokines they express. These subtypes are: IMck1 (Ccl2, Ccl7, Ccl12, a few Cxcl14); IMck2-4 (Ccl3, Ccl4, Ccl5, Cxcl2, Cxcl3); IMck5-7 (Ccl6, Ccl8, Ccl9); IMck8 (Cxcl9, Cxcl10); IMck9 (Cxcl13); and IMck10 (Ccl24). Based on the selective chemokine expression profiles observed, we hypothesized that pulmonary IMs play a critical role in recruiting leukocytes and forming inducible bronchus-associated lymphoid tissue (iBALT) in the lung. First, we examined multiple Cre-expressing mice (Lyve1, Nes, Pdpn, and Pf4) for IM specificity by crossing them with Rosa26EYFP. Only the Pf4Cre mice selectively induced EYFP expression in CD206hiCD64hi IMs, where no other immune cell in the lung expressed EYFP. We then created a CD206hiCD64hi IM-depleting mouse by crossing Pf4Cre with Rosa26DTR and CX3CR1DTR. In a bacterial infection and allergic airway disease, depletion of CD206hiCD64hi IMs resulted in diminished leukocyte recruitment and iBALT formation. Overall, our study highlights the increased granularity in IM populations and demonstrates a division of labor for cellular recruitment and iBALT formation in the lung. Furthermore, the study suggests that the specific combination of chemokines expressed by IMs are tightly regulated, like Th cytokine-producing cells.
2023-03-03 | GSE225662 | GEO
Project description:Lung interstitium macrophages (IMs) are non-alveolar resident tissue macrophages which contribute to the lung homeostasis. These cells were reported to be heterogeneous by our group and other teams, which contains two main distinct subpopulations: CD206+ IMs and CD206- IMs. However, the exact origin of IMs and the transcriptional programs that regulate IM differentiation remains unclear. In recent report, we analyzed the refilled IMs in the course of time after induced IM depletion with single-cell RNA sequencing (10X Genomics Chromium) and bulk RNA sequencing. In this study, the de novo refilled CD206+ and CD206- IMs on Day 14 post-depletion were compared to those without depletion. Alvelar macrophages (AMs) samples were also included in this analysis and served as a reference. Results of clustering and PCA analyses showed high similarity between de novo refilled and original IMs for both CD206+ and CD206- subsets. Only 9 genes were find upregulated in refilled IMs: AA467197, Cd109, Igf2r, Rarb and S100a4.
2023-02-07 | GSE194020 | GEO
Project description:Lung interstitium macrophages (IMs) are non-alveolar resident tissue macrophages which contribute to the lung homeostasis. These cells were reported to be heterogeneous by our group and other teams, which contains two main distinct subpopulations: CD206+ IMs and CD206- IMs. However, the exact origin of IMs and the transcriptional programs that regulate IM differentiation remains unclear. In recent report, we analyzed the refilled IMs in the course of time after induced IM depletion with single-cell RNA sequencing (10X Genomics Chromium) and bulk RNA sequencing. The IMs in Day 4 post-depletion were compared to the those without depletion. Results showed that refilled IMs had a lower ratio of CD206+ IM vs CD206- subpopulation comparing to IMs without depletion, but they shared high similarity to each other, indicating that the de novo IM population had been established before Day 4 post-depletion.
2023-02-07 | GSE193894 | GEO
Project description:Lung interstitium macrophages (IMs) are non-alveolar resident tissue macrophages which contribute to the lung homeostasis. These cells were reported to be heterogeneous by our group and other teams, which contains two main distinct subpopulations: CD206+ IMs and CD206- IMs. However, the exact origin of IMs and the transcriptional programs that regulate IM differentiation remains unclear. In recent report, we analyzed the refilled IMs in the course of time after induced IM depletion with single-cell RNA sequencing (10X Genomics Chromium) and bulk RNA sequencing. The lung IMs and monocytes from the mice at 12 hours (DT12h), 24 hours (DT24h) and 48 hours (DT48h) after diphtheria toxin (DT)-induced IM depletion were analyzed and compared using single-cell RNA sequencing. A subpopulation was found to be a transit differentiating cells from monocytes to IMs. Transcription factor activity analysis and trajectory showed cMAF and MAFb transcription factors played important roles in monocyte-IM differentiation.
2023-02-07 | GSE193896 | GEO