Involvement and targeting of CD206+ macrophages in lymphangioleiomyomatosis.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1167278 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR30841543_1.fastq.gz | Fastqsanger.gz | |||
| SRR30841543_2.fastq.gz | Fastqsanger.gz | |||
| SRR30841544_1.fastq.gz | Fastqsanger.gz | |||
| SRR30841544_2.fastq.gz | Fastqsanger.gz |
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Project description:Lymphangioleiomyomatosis (LAM) is a very rare disease affecting women of childbearing age, either sporadically or in association with tuberous sclerosis complex (TSC). The proliferation of TSC2 null LAM cells in the lung results in cystic destruction, airflow obstruction, respiratory insufficiency and eventually death. In the LAM lung, the tumor immune microenvironment (TME) plays a role in the progression of LAM lesions. Macrophages can be polarized into inflammatory M1 macrophages or protumorigenic immunosuppressive M2 macrophages. Macrophages are an important component of the TME, and we hypothesized that CD206+ M2 macrophages could facilitate LAM progression and represent a potential therapeutic target.
2025-05-29 | GSE278445 | GEO
Project description:Lymphangioleiomyomatosis (LAM) is a progressive neoplastic interstitial lung disease that primarily affects women of reproductive age. It is characterized by the infiltration of the lungs by atypical "LAM" cells, which leads to the cystic destruction of lung tissue. In our study, we employed spatial transcriptomics to analyze cell populations within LAM in order to understand the significance of the spatial organization of LAM cells and macrophages. Each Visium spot covers from one to ten cells. We discovered that some spots have highly expressed macrophage-associated genes (defined as Macro:only) and some highly expressed LAM-associated genes (defined as LAM:only). There are also some spots that have highly expressed both macrophage and LAM markers; we defined these as the LAM_Macro interaction spots. To further understand the spatial organization of LAM and macrophages, we extracted all spots expressing LAM and macrophage-associated genes in our data and examined the molecular profile. In our analysis of PMEL-positive LAM samples, we observed that genes associated with macrophage homing (specifically CCL2, CSF1, CSF2, CXCL12, and IL7) are highly expressed in the LAM:Macro interaction spots. Immunofluorescence analyses showed that CD206+ macrophages are in close proximity to LAM cells in LAM patient lungs. Targeting M2 macrophages via treatment with the CD206 modulator RP-182 impaired the growth of TSC2-deficient tumors in vivo. In conclusion, M2-like CD206high macrophages may represent a potential therapeutic target in LAM.
2025-05-27 | GSE287459 | GEO
Project description:Modulation of infiltrating CD206-positive macrophages restricts progression of pulmonary lymphangioleiomyomatosis (LAM)
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Project description:Macrophages reside in all organs and participate in homeostatic- and immune regulative processes. Little is known about pancreatic macrophage gene expression. CD206 is an endocytic receptor with prior use in subclassifying macrophages. In the present study, global gene expression was characterized in human pancreatic macrophage subpopulations. Flow cytometry was used to sort CD206- and CD206+ macrophages separately from pancreatic islets and exocrine tissue to high purity. RNA-seq generated transcriptomic profiles were then analyzed. Comparing CD206- with CD206+ macrophages, CD206- showed enrichment in proliferation and nucleic acid processing, glycolysis, pro-inflammatory and SPP1-associated gene sets while CD206+ showed enrichment in complement-, IL-10 and IL-2RA immune regulation, as well as scavenging-related gene sets. Two sets involved in immune regulation were enriched in islet CD206-, while various sets including some proinflammatory sets were enriched in exocrine CD206- macrophages. Fewer differences were found between CD206+ macrophages, with enrichment in two IL2-RA related gene sets in islets and eight gene sets in exocrine samples. Comparing macrophages between individuals with normoglycemia, elevated HbA1c or type 2 diabetes, only a few diverse differentially expressed genes were identified. This work characterizes global gene expression and identifies differences between CD206- and CD206+ macrophage populations within the human pancreas.
2025-04-16 | GSE281600 | GEO
Project description:The direct and indirect effects of targeting specific tumor-associated macrophage (TAM) subsets in cancer are not well-defined. TAM targeting strategies are frequently based on the ‘M1’ or ‘M2’ polarization categories, even as substantial data challenges this binary modeling of macrophage cell state. One molecule consistently referenced as a delineator of a putative immunosuppressive ‘M2’ state is the surface protein CD206. We thus made a novel conditional CD206 (Mrc1) knock-in mouse to specifically visualize and/or deplete CD206+ TAMs and assess their correspondence with pro-tumoral immunity. Early, but not late depletion of CD206+ macrophages and monocytes (here, ‘Mono/Macs’) led to an indirect loss of a key anti-tumor network of NK cells, conventional type I dendritic cells (cDC1) and CD8 T cells. Among myeloid cells, we found that the CD206+ TAMs are the primary producers of CXCL9, and able to differentially attract activated CD8 T cells. In contrast, a population of stress-responsive TAMs (“Hypoxic” or Spp1+) and immature monocytes, which lack CD206 expression and become prominent following early depletion, expressed markedly diminished levels of CXCL9. Those NK and CD8 T cells which enter CD206-depleted tumors express vastly reduced levels of the corresponding receptor Cxcr3, the cDC1-attracting chemokine Xcl1 and cDC1 growth factor Flt3l transcripts. Consistent with the loss of this critical network, early CD206+ TAM depletion decreased tumor control by antigen specific CD8 T cells in mice. Likewise, in humans, the CD206Replete, but not the CD206Depleted Mono/Mac gene signature correlated robustly with CD8 T cell, NK cell and stimulatory cDC1 gene signatures and transcriptomic signatures skewed towards CD206Replete Mono/Macs associated with better survival. Together, these findings negate the unqualified classification of CD206+ ‘M2-like’ macrophages as immunosuppressive and provide further evidence of the context-dependence of macrophage function in tumors.
2024-11-08 | GSE281471 | GEO
Project description:CD206 is a common marker of a putative immunosuppressive ‘M2’ state in tumor-associated macrophages (TAMs). We made a novel conditional CD206 (Mrc1) knock-in mouse to specifically visualize and/or deplete CD206+ TAMs. Early depletion of CD206+ macrophages and monocytes (Mono/Macs) led to the indirect loss of conventional type I dendritic cells (cDC1), CD8 T cells and NK cells in tumors. CD206+ TAMs robustly expressed CXCL9, contrasting with stress-responsive Spp1-expressing TAMs and immature monocytes, which became prominent with early depletion. CD206+ TAMs differentially attracted activated CD8 T cells, and the NK and CD8 T cells in CD206-depleted tumors were deficient in Cxcr3, and cDC1-supportive Xcl1 and Flt3l expression. Disrupting this key anti-tumor axis decreased tumor control by antigen-specific T cells in mice. In human cancers, a CD206Replete, but not a CD206Depleted Mono/Mac gene signature correlated robustly with CD8 T cell, cDC1 and NK signatures, and associated with better survival. These findings negate the unqualified classification of CD206+ ‘M2-like’ macrophages as immunosuppressive.
2024-11-08 | GSE281345 | GEO
Project description:Targeting CD206+ macrophages disrupts the establishment of a key anti-tumor immune axis
| PRJNA1183905 | ENA
Project description:Transcriptomic characterization of CD206- and CD206+ macrophages in human pancreatic islets and exocrine tissue
| PRJNA1184777 | ENA
Project description:Targeting CD206+ macrophages disrupts the establishment of a key anti-tumor immune axis [scRNA-seq]
| PRJNA1183420 | ENA
Project description:BACKGROUND & AIMS: Intestinal mononuclear phagocytes (MNP) are phenotypically similar, but have different functions. Macrophages contribute to the pathogenesis of inflammatory bowel disease (IBD). To understand this contribution it is necessary to distinguish macrophages from other MNPs, and identify functionally-different macrophage populations. We aimed to accurately identify intestinal macrophage populations, and to ascertain their functions in patients with inflammatory bowel disease (IBD). METHODS: We developed 12-parameter flow cytometry protocols to identify and characterise human intestinal MNPs. We then used RNA sequencing, qPCR, and flow cytometry to analyse colonic biopsies from patients with CD, UC, or non-inflamed controls, in a cross-sectional study. RESULTS: We unambiguously differentiate macrophage populations (CD45+CD64+ HLA-DR+) from dendritic cells (CD45+CD64- HLA-DR+ CD11c;). We identify two distinct subsets within the macrophage population, differentiated by their expression of the mannose receptor, CD206. Further examination of these macrophage sub-populations showed that CD206+ macrophages expressed markers consistent with a mature macrophage phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of Trem1. On the contrary, CD64+ HLA-DR- CD206- cells appear to be semi-mature intermediaries in the development of mature intestinal macrophages from their monocyte precursors. CONCLUSIONS: We identified and purified MNP and macrophage populations from human intestinal lamina propria. Thorough characterisation reveals that human colonic macrophages appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature they lose their proliferative properties and acquire expression of IL-10, CD206, CD63, and CD168. Targeting the newly recruited monocyte-derived cells may represent a fruitful avenue to ameliorate chronic inflammation in IBD.
2018-12-26 | GSE124350 | GEO