AT2-Derived GM-CSF Promotes CD301b⁺ cDC2 Generation and Type 2 Inflammation in the Lung
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1255205 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pulmonary conventional dendritic cells (cDCs) are functionally and phenotypically heterogeneous antigen-presenting cells essential for orchestrating adaptive immune responses in the lung. Here, we define a critical role for granulocyte-macrophage colony-stimulating factor (GM-CSF) in generating a CD301b+ subset of terminally differentiated cDC2s. GM-CSF signaling is intrinsically required for their development, independent of GM-CSF-dependent alveolar macrophages. Absence of GM-CSF results in a defect similar to that seen in CD103+XCR1+ cDC1s. Unbiased single-cell transcriptomic profiling of CD11c+ cells identified both immature and differentiated cDC populations. GM-CSF deficiency disrupted anti-apoptotic Bcl2a1 upregulation and impaired progression to the CD301b+ transcriptional state. Despite their positioning in lymphoid cell-rich adventitial cuff areas, hematopoietic GM-CSF was dispensable. Instead, genetic GM-CSF gain- and loss-of-function studies showed that alveolar epithelial type 2 cell-derived GM-CSF is required for CD301b+ cDC2 formation and pulmonary type 2 immune responses, highlighting the central role of GM-CSF signaling in shaping the pulmonary myeloid landscape.
2025-08-04 | GSE295575 | GEO
Project description:Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. Multiple factors including cytokines, transcription factors and multiple signaling pathways are involved in MDSC differentiation. Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin(IL-6) etc could in vitro mediate development of MDSCs.IL-6 with GM-CSF mediated MDSC not only had stronger suppressive function but also the dynamics of their suppressive function was different from GM-CSF alone mediated MDSCs.To found a new regulatory factor (s) in tumor and inflammatory environments, we compared GM-CSF and IL-6 mediated MDSCs with GM-CSF alone mediated MDSCs using lncRNA microarray, miRNA microarrays and protein-coding mRNA microarrays.
2017-10-09 | GSE104719 | GEO
Project description:Lipopolysaccharide (LPS) can either promote or prevent T helper-2 (Th2) cell-allergic responses. However, the underlying mechanism remains unknown. We show here that LPS activity switches from pro-pathogenic to protective depending on the production of GM-CSF by non-classical monocytes. In the absence of GM-CSF, LPS can favor pathogenic Th2 cell responses by supporting the trafficking of lung migratory dendritic cells (mDC2s) into the lung-draining lymph node. However, when non-classical monocytes produce GM-CSF, LPS and GM-CSF synergize to differentiate monocyte-derived DCs (moDCs) that instruct mDC2s for Th2 cell suppression. Importantly, only allergens with cysteine protease activity trigger GM-CSF production by non-classical monocytes. Hence, the therapeutic effect of LPS is restricted to allergens with this enzymatic activity. Treatment with GM-CSF, however, restores the protective effects of LPS. Thus, GM-CSF produced by non-classical monocytes acts as a rheostat that fine-tunes the pathogenic and therapeutic functions of LPS.
2021-12-06 | GSE186449 | GEO
Project description:Bone marrow cells were isolated, primed with M-CSF (M-BMDM) or GM-CSF (GM-BMDM) and cultured for 7 days. The proteomic difference between GM-BMDM and M-BMDM were analyzed to describe the phenotye and function of two types of macrophages.
2023-03-29 | PXD041180 |
Project description:Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. Multiple factors including cytokines, transcription factors and multiple signaling pathways are involved in MDSC differentiation. Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin(IL-6) etc could in vitro mediate development of MDSCs.IL-6 with GM-CSF mediated MDSC not only had stronger suppressive function but also the dynamics of their suppressive function was different from GM-CSF alone mediated MDSCs.To found a new regulatory factor (s) in tumor and inflammatory environments, we compared GM-CSF and IL-6 mediated MDSCs with GM-CSF alone mediated MDSCs using lncRNA microarray and protein-coding mRNA microarrays.
2017-10-09 | GSE104718 | GEO
Project description:Human and murine studies showed that granulocyte macrophage colony-stimulating factor (GM-CSF) exerts beneficial effects in intestinal inflammation. To explore whether GM-CSF mediates its effects via monocytes, we analyzed effects of GM-CSF on monocytes in vitro and assessed the immunomodulatory potential of GM-CSF-activated monocytes (GMaM). We used microarray technology and functional assays to characterize GMaM in vitro and used a mouse model of colitis to study GMaM functions in vivo.
2014-11-27 | GSE63662 | GEO
Project description:Using single-cell RNA sequencing (10X technology) on CD4+T cells, we report that GM-CSF-activated human blood CD1c+ dendritic cells (DC) (cDC2) drive the differentiation of naïve CD4+ T cells into Tfh1. These Tfh1 cells displayed typical Tfh molecular features, including high levels of PD-1, CXCR5, and ICOS. They co-expressed Bcl6 and T-bet, and secreted large amounts of IL-21 and IFN-γ.
2022-10-01 | GSE167364 | GEO
Project description:GM-CSF is involved in immune complex (IC)-mediated arthritis. However, little is known about what is the cellular source of GM-CSF and how it is regulated during IC-mediated inflammation. Using novel GM-CSF reporter mice, we show that NK cells produce GM-CSF during an IC-mediated model of inflammatory arthritis. NK cells promoted STIA in a GM-CSF-dependent manner, as deletion of NK cells and selective removal of GM-CSF production by NK cells abrogated disease. Furthermore, we show that myeloid cell activation by GM-CSF is restrained by induction of JAK/STAT checkpoint inhibitor cytokine-inducible SH2-containing protein, CIS. Myeloid cells from CIS-deficient mice had exaggerated responses to GM-CSF, and these mice develop exacerbated STIA. Our data suggest that tissue NK cells may amplify joint inflammation in arthritis via GM-CSF production and thus represent a novel target in IC-mediated pathology. Endogenous CIS provides a key brake on signaling through the GM-CSF receptor and strategies that boost its function may provide an alternative anti-inflammatory approach.
2020-02-19 | PXD012794 | Pride
Project description:Systemic GM-CSF promotes myelopoiesis and inflammation and GM-CSF blockade is being evaluated as treatment for COVID-19-associated hyperinflammation. Alveolar GM-CSF is however required for monocytes to differentiate into alveolar macrophages (AM) that control alveolar homeostasis and dampen inflammation. By mapping cross-species AM development stages to clinical lung samples, we discovered that COVID-19 is marked by defective GM-CSF-dependent AM instruction and accumulation of proinflammatory macrophages. In a multi-center, open-label, randomized, controlled trial in 81 non-ventilated COVID-19 patients with respiratory failure, we found that inhalation of rhu-GM-CSF did not improve mean oxygenation parameters compared with standard treatment. However, more patients on GM-CSF had a clinical response, and GM-CSF inhalation induced higher numbers of virus-specific CD8 effector lymphocytes and class-switched B cells, without exacerbating systemic hyperinflammation. This translational proof-of-concept study provides rationale for further testing of inhaled GM-CSF as non-invasive treatment to improve alveolar gas exchange and simultaneously boost anti-viral immunity in COVID-19
2022-11-03 | GSE216704 | GEO
Project description:Analysis of genes induced in DC precursors and in BM cells and monocytes treated with GM-CSF For progenitor arrays, bone marrow progenitors (CMP, GMP, CDP, and pre-cDC) were harvested from WT C57Bl/6 mice. For culture arrays, BM was cultured in the presence of GM-CSF or M-CSF and adherent and non-adherent cells sorted. For monocyte cultures, sorted BM monocytes were treated with GM-CSF for 0, 24 or 48 hours.
2012-05-20 | E-GEOD-37029 | biostudies-arrayexpress