Early Life Inflammation Primes a Th2-Fibroblast Niche in Skin
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA758894 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15668550.fastq.gz | Fastqsanger.gz | |||
| SRR15668551.fastq.gz | Fastqsanger.gz | |||
| SRR15668552.fastq.gz | Fastqsanger.gz | |||
| SRR15668553.fastq.gz | Fastqsanger.gz | |||
| SRR15668554.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Inflammation early in life can prime the local immune milieu of peripheral tissues, causing lasting changes in immunologic tone that confer disease protection or susceptibility. The cellular and molecular mechanisms that incite changes in immune tone in many nonlymphoid tissues remain largely unknown. We find that time-limited neonatal inflammation induced by transient reduction of neonatal regulatory T cells (Tregs) causes a dramatic dysregulation of subcutaneous tissue in murine skin, accompanied by the selective accumulation of Th2 cells within a distinct microanatomic niche. Th2 cells are maintained into adulthood through interactions with a fibroblast population in skin fascia that we refer to as Th2-interacting fascial fibroblasts (TIFFs), which expand in response to Th2 cytokines to form subcutaneous fibrous bands. Activation of the Th2-TIFF niche by neonatal inflammation primes skin for altered reparative responses to wounding. We further identify fibroblasts in healthy human skin expressing the TIFF transcriptional signature and find these cells at high levels in eosinophilic fasciitis, an orphan disease characterized by inflammation and fibrosis of the skin fascia. Taken together, these data define a novel Th2 niche in skin, functionally characterize a disease-associated fibroblast population, and suggest a mechanism of immunologic priming whereby inflammation early in life creates networks between adaptive immune cells and stromal cells, establishing an immunological set-point in tissues that is maintained throughout life.
2021-10-01 | GSE183031 | GEO
Project description: Not available
| S-EPMC8906225 | biostudies-literature
Project description:Local fibroblast development and densities greatly influence organ health and disease, although it remains unclear how tissue fibroblast topography is controlled in situ. Here we define group 2 innate lymphoid cells (ILC2) as key regulators of fibroblast homeostasis in the pancreas. ILC2 co-localise with Pi16+Dpp4+Ly6c+ fibroblasts in an interstitial niche of the exocrine pancreas, which encapsulates the organ parenchyma. ILC2 specifically regulate the expansion of Pi16+Dpp4+Ly6c+ fibroblasts, which have progenitor capacity, while paradoxically also restraining differentiated intra-parenchymal Col15a1+ fibroblasts during inflammation. These homeostatic circuits reinforce fibroblast numbers after injury and set an inflammatory threshold. The ILC2-Pi16+Dpp4+Ly6c+ fibroblast progenitor niche expands locally in cancer, and controls cancer associated fibroblast ontogeny and density. Hence, ILC2-fibroblast dialogue represents a regulatory node that locally orchestrates tissue homeostasis and pathology.
2026-07-03 | GSE308872 | GEO
Project description:Pancreatic cancer is associated with a high rate of metastasis and poor prognosis. The formation of a premetastatic niche (PMN) facilitates cancer cell spread and contributes to cancer mortality. Using murine pancreatic cancer models based on expression of oncogenic KRAS in the pancreas epithelium, we discovered that remodeling of the lung microenvironment occurred in mice bearing pancreatic precursor lesions prior to cancer formation. This early lesion premetastatic niche (EL-PMN) resembled the PMN in cancer-bearing mice, and both feature characteristics of overt metastasis, such as transcriptional reprogramming, activation of fibroblast STAT3 signaling, and infiltration of immunosuppressive ARG1+ macrophages. Both pancreatic cancer patients and mouse models demonstrated elevated serum IL6. Inactivating oncogenic KRAS reduced serum IL6 and reverted fibroblast STAT3 phosphorylation in mouse lungs; loss of lung fibroblast STAT3 phosphorylation was similarly observed when mice were treated with the pan-RAS inhibitor RMC7977. While ARG1+ macrophage infiltration was dispensable for fibroblast STAT3 activation, IL6 blockade inhibited lung fibroblast STAT3 activation. Functionally, fibroblast STAT3 activation was necessary for lung metastasis establishment and growth. Interestingly, activation of STAT3 in the PMN was present in the lungs but not in the liver, where fibroblast reprogramming occurred only in overt metastasis, pointing to organ-specific PMN formation. In human metastasis samples, phosphorylated STAT3 in fibroblasts was similarly more abundant in the lungs than liver. Together, these data point to organ-specific mechanisms driving formation of the PMN and indicate that reprogramming of the microenvironment prior to metastasis might support early dissemination of pancreatic cancer.
2025-10-07 | GSE292712 | GEO
Project description:Fibroblast STAT3 activation drives organ-specific premetastatic niche formation
| PRJNA1241135 | ENA
Project description:Local fibroblast development and densities underpin their role in regulating organ function and inflammation, although it remains unclear how tissue fibroblast topography is controlled in situ. Here we define group 2 innate lymphoid cells (ILC2) as key regulators of fibroblast homeostasis in the pancreas. We show that ILC2 co-localise with Pi16+Dpp4+Ly6c+Il33+ fibroblast progenitors in an interstitial niche of the exocrine pancreas, which demarcates and encapsulates the organ parenchyma. ILC2 specifically regulate the expansion of this progenitor population, while paradoxically also restraining differentiated intra-parenchymal Col15a1+ fibroblasts under inflammatory conditions. These homeostatic circuits reinforce fibroblast numbers after injury and set an inflammatory threshold at steady-state. Hence, ILC2-fibroblast dialogue represents a regulatory node that locally orchestrates tissue homeostasis and pathology.
2026-07-03 | GSE248384 | GEO
Project description:Local fibroblast development and densities underpin their role in regulating organ function and inflammation, although it remains unclear how tissue fibroblast topography is controlled in situ. Here we define group 2 innate lymphoid cells (ILC2) as key regulators of fibroblast homeostasis in the pancreas. We show that ILC2 co-localise with Pi16+Dpp4+Ly6c+Il33+ fibroblast progenitors in an interstitial niche of the exocrine pancreas, which demarcates and encapsulates the organ parenchyma. ILC2 specifically regulate the expansion of this progenitor population, while paradoxically also restraining differentiated intra-parenchymal Col15a1+ fibroblasts under inflammatory conditions. These homeostatic circuits reinforce fibroblast numbers after injury and set an inflammatory threshold at steady-state. Hence, ILC2-fibroblast dialogue represents a regulatory node that locally orchestrates tissue homeostasis and pathology.
2026-07-03 | GSE248383 | GEO
Project description:Local fibroblast development and densities underpin their role in regulating organ function and inflammation, although it remains unclear how tissue fibroblast topography is controlled in situ. Here we define group 2 innate lymphoid cells (ILC2) as key regulators of fibroblast homeostasis in the pancreas. We show that ILC2 co-localise with Pi16+Dpp4+Ly6c+Il33+ fibroblast progenitors in an interstitial niche of the exocrine pancreas, which demarcates and encapsulates the organ parenchyma. ILC2 specifically regulate the expansion of this progenitor population, while paradoxically also restraining differentiated intra-parenchymal Col15a1+ fibroblasts under inflammatory conditions. These homeostatic circuits reinforce fibroblast numbers after injury and set an inflammatory threshold at steady-state. Hence, ILC2-fibroblast dialogue represents a regulatory node that locally orchestrates tissue homeostasis and pathology.
2026-07-03 | GSE248385 | GEO
Project description:Local fibroblast development and densities underpin their role in regulating organ function and inflammation, although it remains unclear how tissue fibroblast topography is controlled in situ. Here we define group 2 innate lymphoid cells (ILC2) as key regulators of fibroblast homeostasis in the pancreas. We show that ILC2 co-localise with Pi16+Dpp4+Ly6c+Il33+ fibroblast progenitors in an interstitial niche of the exocrine pancreas, which demarcates and encapsulates the organ parenchyma. ILC2 specifically regulate the expansion of this progenitor population, while paradoxically also restraining differentiated intra-parenchymal Col15a1+ fibroblasts under inflammatory conditions. These homeostatic circuits reinforce fibroblast numbers after injury and set an inflammatory threshold at steady-state. Hence, ILC2-fibroblast dialogue represents a regulatory node that locally orchestrates tissue homeostasis and pathology.
2026-07-03 | GSE248386 | GEO
Project description:Pericryptal myofibroblasts in the colon and rectum play an important role in regulating the normal colorectal stem cell niche and facilitating tumour progression. Myofibroblasts have previously mostly been distinguished from normal fibroblasts only by the expression of α smooth muscle actin (αSMA). We now identify AOC3, a surface monoamine oxidase, as a new marker of myofibroblasts by showing that it is the target protein of the myofibroblast reacting monoclonal antibody (mAb), PR2D3. The normal and tumour tissue distribution and the cell line reactivity of AOC3 match that expected for myofibroblasts. We have shown that the surface expression of AOC3 is sensitive to digestion by trypsin and collagenase and that anti-AOC3 antibodies can be used for FACS sorting of myofibroblasts obtained by non-enzymatic procedures. Whole genome microarray mRNA expression profiles of myofibroblasts and skin fibroblasts revealed four additional genes that are significantly expressed differentially between these two cell types; NKX2-3 and LRRC17 are expressed in myofibroblasts and SHOX2 and TBX5 in skin fibroblasts. Transforming Growth Factor β (TGFβ) substantially down-regulated AOC3 expression in myofibroblasts but not in skin fibroblasts, in which it dramatically increased the expression of αSMA. A knockdown of NKX2-3 in myofibroblasts caused a decrease of myofibroblast-related gene expression and an increased expression of the fibroblast associated gene, SHOX2, suggesting that NKX2-3 is a key mediator for maintaining myofibroblast characteristics. Our results show that colorectal myofibroblasts, as defined by the expression of AOC3, NKX2-3 and other markers, are a distinctly different cell type from TGFβ activated fibroblasts. colorectal myofibroblast specific markers and expression profiles were sought by comparing four primary myofibroblast cultures to a panel of four dermal and foreskin fibroblast cell lines Four primary myofibroblast cultures established from adult human colon compared to four skin fibroblast cell lines to identify intestinal myofibroblast specific markers
2016-04-06 | E-GEOD-77474 | biostudies-arrayexpress