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Gene expression profiles of the lung of CD2-T-bet transgenic mice

ABSTRACT: To uncover potential mechanisms underlying the observed Pulmonary Alveolar Proteinosis-like phenotype, we performed a microarray analysis using lung mRNAs from T-bet transgenic mice. Gene expression signatures associated with pulmonary alveolar proteinosis induced by T-bet overexpression in T cells were measured.

ORGANISM(S): Mus musculus

SUBMITTER: Shin Kaneko

PROVIDER: E-GEOD-62637 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression profiles of the lung of CD2-T-bet transgenic mice

Project description:To uncover potential mechanisms underlying the observed Pulmonary Alveolar Proteinosis-like phenotype, we performed a microarray analysis using lung mRNAs from T-bet transgenic mice.

2014-11-03 | GSE62637 | GEO

Transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function.

Project description:Pulmonary alveolar proteinosis (PAP) results from a dysfunction of alveolar macrophages (AMs), chiefly due to disruptions in the signaling of granulocyte macrophage colony-stimulating factor (GM-CSF). We found that mice deficient for the B lymphoid transcription repressor BTB and CNC homology 2 (Bach2) developed PAP-like accumulation of surfactant proteins in the lungs. Bach2 was expressed in AMs, and Bach2-deficient AMs showed alterations in lipid handling in comparison with wild-type (WT) cells. Although Bach2-deficient AMs showed a normal expression of the genes involved in the GM-CSF signaling, they showed an altered expression of the genes involved in chemotaxis, lipid metabolism, and alternative M2 macrophage activation with increased expression of Ym1 and arginase-1, and the M2 regulator Irf4. Peritoneal Bach2-deficient macrophages showed increased Ym1 expression when stimulated with interleukin-4. More eosinophils were present in the lung and peritoneal cavity of Bach2-deficient mice compared with WT mice. The PAP-like lesions in Bach2-deficient mice were relieved by WT bone marrow transplantation even after their development, confirming the hematopoietic origin of the lesions. These results indicate that Bach2 is required for the functional maturation of AMs and pulmonary homeostasis, independently of the GM-CSF signaling. WT (n=8) and Bach2KO (n=3) AMs. One expreriment was performed.

2014-01-15 | E-GEOD-54050 | biostudies-arrayexpress

Project description:GM-CSF receptor-Î² deficient (Csf2rbâ/â or KO) mice develop a lung disease identical to hereditary pulmonary alveolar proteinosis (hPAP) in humans with recessive CSF2RA or CSF2RB mutations that impair GM-CSF receptor function. We performed pulmonary macrophage transplantation (PMT) of bone marrow derived macrophages (BMDMs) without myeloablation in Csf2rbâ/âmice. BMDMs were administered by endotracheal instillation into 2 month-old Csf2rbâ/â mice. Results demonstrated that PMT therapeutic of hPAP in Csf2rbâ/â mice was highly efficacious and durable. Alveolar macrophages were isolated by bronchoalveolar lavage one year after administration subjected to microarray analysis to determine the effects of PMT therapy on the global gene expression profile. Total mRNA was isolated from alveolar macrophages PMT-treated Csf2rbâ/âmice (PMT) and from age-matched, untreated KO mice (KO) and wild-type (C57Bl/6) mice (WT). Total mRNA was evaluated using Affymetrix microarrays (Mouse Gene 1.0 ST Array) to compare the gene expression profiles among the three groups (3 mice/group).

2014-10-01 | E-GEOD-60528 | biostudies-arrayexpress

Project description:GM-CSF receptor-β deficient (Csf2rb–/– or KO) mice develop a lung disease identical to hereditary pulmonary alveolar proteinosis (hPAP) in humans with recessive CSF2RA or CSF2RB mutations that impair GM-CSF receptor function. We performed pulmonary macrophage transplantation (PMT) of bone marrow derived macrophages (BMDMs) without myeloablation in Csf2rb–/–mice. BMDMs were administered by endotracheal instillation into 2 month-old Csf2rb–/– mice. Results demonstrated that PMT therapeutic of hPAP in Csf2rb–/– mice was highly efficacious and durable. Alveolar macrophages were isolated by bronchoalveolar lavage one year after administration subjected to microarray analysis to determine the effects of PMT therapy on the global gene expression profile.

2014-10-01 | GSE60528 | GEO

Menin orchestrates macrophage reprogramming to maintain the pulmonary immune homeostasis [RNA-seq]

Project description:Menin is a scaffold protein encoded by the Men1 gene, and it interacts with a variety of chromatin regulators to activate or repress cellular processes. The potential importance of menin in immune regulation remains unclear. Here, we report that myeloid deletion of Men1 results in the development of spontaneous pulmonary alveolar proteinosis (PAP). This is strongly correlated with impaired development of alveolar macrophages (AM) and epigenetic inactivation of the GM-CSF pathway caused by Men1 deficiency. Mechanistically, menin directly interacts with SETD2 through the NTD and Palm domains to maintain protein stability and chromatin recruitment. SETD2 and menin collectively maintain GM-CSF expression through H3K36me3, which orchestrates AM reprogramming and pulmonary immune homeostasis.

2024-08-31 | GSE265805 | GEO

Multicenter International Retrospective Cross-sectional Evaluation of Pulmonary Alveolar Proteinosis (MICEPAP) Trial - RLD 5706

Project description:Multicenter International Retrospective Cross-sectional Evaluation of Pulmonary Alveolar Proteinosis (MICEPAP) Trial - RLD 5706

| PRJNA377201 | ENA

Homo sapiens

Project description:Multicenter International Retrospective Cross-sectional Evaluation of Pulmonary Alveolar Proteinosis (MICEPAP) Trial - RLD 5706

| PRJNA377202 | ENA

Development of gene expression signatures for ANP in HUVEC

Project description:Analysis of HUVEC treated with ANP. ANP is a cardiac hormone, binding to the guanylate cyclase-A (GC-A) receptor with a major role in cardiovascular homeostatic mechanisms. Results provide insight into the molecular mechanisms of ANP in vascular endothelial cell. ANP induced gene expression in HUVEC was measured at 0, 1 and 6 hours. Four independent experiments were performed at each time (0, 1 or 6 hours) for each experiment.

2014-04-23 | E-GEOD-56976 | biostudies-arrayexpress

Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals

Project description:As a starting point for exploring potential differences in gene expression between conventional NK and FcRÎ³-NK cells, and to screen for genes that might contribute to the enhanced CD16 responsiveness of g-NK cells, we performed gene expression profiling studies on sorted samples of NK cells. NKG2C, NCR, and KIR surface receptors were used to separate FcRÎ³- NK and conventional NK cells. Indicated subsets of NK cells were sorted from 4 individual donors using a two-way sorter. RNA extracted from the sorted enriched samples were treated with Dnase and analyzed by DNA microarray (Agilent).

2015-02-20 | E-GEOD-66124 | biostudies-arrayexpress

MICEPAP Trial

Project description:<p>The purpose of this study is to (1) compare a technically improved assay with an existing assay used to measure serum anti-GM-CSF antibodies in stored serum samples previously obtained from patients diagnosed with either primary, secondary, congenital or idiopathic pulmonary alveolar proteinosis (PAP), other chronic diseases or disease-free, healthy individuals; (2) determine the prevalence and levels of anti-GM-CSF autoantibodies and (3) define the breadth of the autoimmune antibody responses in primary PAP patients from the United States, Japan, Australia, and Europe using previously collected serum samples; and (4) using a chart review approach, compare the clinical, radiologic and laboratory features of primary PAP patients to determine if differences exist among patients in these globally geographically distributed regions.</p>

| phs001309 | dbGaP

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