Immunologically active mycobiome in children with beta cell autoimmunity
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ABSTRACT:
PROVIDER: PRJNA420169 | ENA |
REPOSITORIES: ENA
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Project description:Immunologically active microbiome in children with beta cell autoimmunity Raw sequence reads
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Project description:The gastrointestinal ecosystem is a highly complex environment with a profound influence on human health. Inflammation in the gut, linked to an altered gut microbiome has been associated with the development of multiple human conditions including type 1 diabetes (T1D). Viruses infecting the gastrointestinal tract, especially enteroviruses, are also thought to play an important role in T1D pathogenesis possibly via overlapping mechanisms. Here, we apply an integrative approach to combine comprehensive faecal virome, microbiome and metaproteome data sampled before and at the onset of islet autoimmunity in 40 children. We show strong age and antibody related effects across the datasets. Mastadenovirus infection was associated with profound functional changes in the faecal metaproteome. Multiomic factor analysis modelling revealed proteins associated with carbohydrate transport from the genus Faecalibacterium were associated with islet autoimmunity. These findings demonstrate functional remodelling of the gut microbiota accompanies both islet autoimmunity and viral infection.
2022-08-22 | PXD032997 | Pride
Project description:The oral mycobiome of children with and without dental caries
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Project description:TH2 and innate lymphoid cells 2 (ILC2) can stimulate tumor growth by secreting pro-tumorigenic cytokines such as IL4, IL5 and IL13. However, the mechanisms by which type 2 immune cells traffic to the tumor microenvironment (TME) are unknown. Here, in pancreatic ductal adenocarcinoma (PDAC), we show that oncogenic KrasG12D (Kras*) increases the expression of IL33 in cancer cells, which upon secretion recruits and activates the TH2 and ILC2. Correspondingly, cancer cell-specific deletion of IL33 reduces TH2 and ILC2 recruitment and promotes tumor regression. Unexpectedly, we discovered that the cellular release of IL33 into the TME is dependent on the intratumoral fungal mycobiome. Genetic deletion of IL33 or anti-fungal treatment decreases TH2 and ILC2 infiltration and increases survival. Consistent with these murine data, high IL33 expression is observed in approximately 20% of human PDAC, and expression is mainly restricted to cancer cells. These data expand our knowledge of the mechanisms driving PDAC tumor progression and identifies therapeutically targetable pathways involving intratumoral mycobiome-driven secretion of IL33.
2022-03-01 | GSE190103 | GEO
Project description:We report the RNAseq of mouse pancreatic cancer cell lines with Kras ON vs Kras OFF. TH2 and innate lymphoid cells 2 (ILC2) can stimulate tumor growth by secreting pro-tumorigenic cytokines such as IL4, IL5 and IL13. However, the mechanisms by which type 2 immune cells traffic to the tumor microenvironment (TME) are unknown. Here, in pancreatic ductal adenocarcinoma (PDAC), we show that oncogenic KrasG12D (Kras*) increases the expression of IL33 in cancer cells, which upon secretion recruits and activates the TH2 and ILC2. Correspondingly, cancer cell-specific deletion of IL33 reduces TH2 and ILC2 recruitment and promotes tumor regression. Unexpectedly, we discovered that the cellular release of IL33 into the TME is dependent on the intratumoral fungal mycobiome. Genetic deletion of IL33 or anti-fungal treatment decreases TH2 and ILC2 infiltration and increases survival. Consistent with these murine data, high IL33 expression is observed in approximately 20% of human PDAC, and expression is mainly restricted to cancer cells. These data expand our knowledge of the mechanisms driving PDAC tumor progression and identifies therapeutically targetable pathways involving intratumoral mycobiome-driven secretion of IL33.
2022-03-01 | GSE190468 | GEO
Project description:Immunotherapy in immunologically active tumors may improve prognosis of non-small cell lung carcinomas (NSCLC). Our objective was to develop a reliable and stable scoring system for the identification of immunologically active HNSCC and to evaluate its association with response to immunotherapies. A Hot Oral Tumor (HOT) score was developed using data from The Cancer Genome Atlas in human-papillomavirus negative head and neck squamous cell carcinomas; it was computed in 92 patients with early stage NSCLC treated with surgery to evaluate the prognostic impact of the HOT score.
2022-07-07 | GSE162520 | GEO
Project description:Type 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western countries. Earlier metabolomics studies suggest that T1D is preceded by dysregulation of lipid metabolism. Here we used a lipidomics approach to analyze molecular lipids in a prospective series of 428 plasma samples from 40 children who progressed to T1D (PT1D), 40 children who developed at least a single islet autoantibody but did not progress to T1D during the follow-up (P1Ab) and 40 matched controls (CTR). Sphingomyelins were found to be persistently downregulated in PT1D when compared to the P1Ab and CTR groups. Triacylglycerols and phosphatidylcholines were mainly downregulated in PT1D as compared to P1Ab at the age of 3 months. Our study suggests that children who progressed to islet autoimmunity or overt T1D are characterized by distinct lipidomic signatures, which may be helpful in the identification of at-risk children before the initiation of autoimmunity.
2018-07-16 | MTBLS620 | MetaboLights