Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A maternally inherited polymorphism in mitochondrial genome alters immune cell metabolism and protects mice from skin inflammation

ABSTRACT: Several mitochondrial genetic variants have been associated with different chronic inflammatory diseases. However, experimental proof for the pathogenic relevance of these associations is still missing. We have reported that polymorphisms in the mitochondrial gene MT-ATP8, which encodes a subunit of the mitochondrial ATP synthase, are associated with the autoimmune skin disease bullous pemphigoid. Using a mouse model for this disease, we show here that a SNP in mt-Atp8 determine the severity of autoantibody-induced skin inflammation by modulating T effector cell function and shifting the levels of short chain fatty acids. With respect to the latter, increased levels of propionate are associated with milder disease, and systemic administration of propionate ameliorates disease. By employing the Aldara™-induced psoriasiform dermatitis model, we further demonstrate that the immunomodulatory effects of mt-Atp8 variants are also relevant for autoinflammation. Collectively, our results highlight discrete mitochondrial genetic variants as significant general modulators of skin inflammation and possibly of other organs.

ORGANISM(S): Mus musculus

PROVIDER: GSE126956 | GEO | 2020/02/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data from IMQ-induced psoriasis-like skin inflammation in miR-146a-/- and C57BL6J mice

Project description:miR-146a acts as a negative feedback regulator of inflammation. To investigate the role of miR-146a in psoriasis psoriasiform skin inflammation was indeuced in Mir-146a-/- and wild type mice (C57BL6J) by topical applciation of imiquimod (IMQ)-cream (Aldara). Gene expression profiling (Affymetrix) was used to identify transcriptomic changes associated with psoriasis-like skin inflammation in wild type vs. miR-146a -/-mice. A daily topical dose of 31.25 mg of Aldara cream (5% IMQ) was applied on the right ear of miR-146a -/- and C57BL/6 mice on three consecutive days to induce psorisis-like skin inflammation. Mice were sacrificed at day 4. Ear flaps were collected for total RNA extraction and hybridization on Affymatrix GeneTitan plate format Gene ST 2.1 (mouse).

2016-02-19 | E-GEOD-78057 | biostudies-arrayexpress

Bulk RNA-seq of primary keratinocytes treated with IgG from patients with bullous pemphigoid or controls II

Project description:While antibodies in bullous pemphigoid (BP) are known to activate innate immune response, their direct effect on keratinocytes and the overall contribution of keratinocytes to disease pathogenesis is largely unknown. We sought to understand the mechanism of keratinocyte response to autoantibodies in BP. We affinity purified IgG from patients with a known diagnosis of bullous pemphigoid or healthy controls, and performed bulk RNA-seq. We identified numerous differentially expressed genes including upregulation of CXCL16, IL-24, and TGFB1 in BP-IgG treated keratinocytes

2024-12-04 | GSE280620 | GEO

Bulk RNA-seq of primary keratinocytes treated with IgG from patients with bullous pemphigoid or controls I

2024-12-04 | GSE280619 | GEO

Expression data from IMQ-induced psoriasis-like skin inflammation in miR-146a-/- and C57BL6J mice

2016-02-19 | GSE78057 | GEO

Skin metagenome

Project description:Characterization of the skin microbiome in patients with bullous pemphigoid

| PRJNA715468 | ENA

BP180 dysfunction triggers spontaneous skin inflammation in mice

Project description:BP180, also known as collagen XVII, is a hemidesmosomal component and plays a key role in 2 maintaining skin dermal/epidermal adhesion. Dysfunction of BP180, either through genetic 3 mutations in Junctional Epidermolysis Bullosa (JEB) or autoantibody insult in Bullous Pemphigoid 4 (BP), leads to subepidermal blistering accompanied by skin inflammation. However, whether BP180 5 is involved in skin inflammation remains unknown. To address this question, we generated a BP180-6 dysfunctional mouse strain and found that mice lacking functional BP180 (termed ΔNC16A) 7 developed spontaneous skin inflammatory disease, characterized by severe itch, defective skin 8 barrier, infiltrating immune cells, elevated serum IgE levels and increased expression of thymic 9 stromal lymphopoietin (TSLP). Severe itch is independent of adaptive immunity and histamine, but 10 dependent on increased expression of TSLP by keratinocytes. Our data provide the first direct 11 evidence showing that BP180 regulates skin inflammation independently of adaptive immunity, and 12 BP180 dysfunction leads to a TSLP mediated itch.

2018-03-23 | GSE112235 | GEO

Human gut

Project description:The gut microbiome in bullous pemphigoid

| PRJNA954584 | ENA

Interleukin 2 distinctly activates human basophils in skin disorders

Project description:Basophils are important effector cells in allergic inflammation, anti-parasitic immune response and skin disorders. A number of activators including interleukin 3 (IL-3) and IgE have been identified in the regulation of human basophils expressing mediators such as histamine and leukotriene C4 (LTC4) and cytokines, including IL-4 and IL-13. Human basophils express high levels of IL-2 receptors. However, the function of the IL-2 pathway in basophils remains unknown. Here, we identify that IL-2-stimulated human basophils in vitro express a variety of inflammatory cytokines and chemokines including IL-5, IL-13, GM-CSF and CCL-17. Of note, one of the top regulated cytokines, IL-5, was for the first time identified to be expressed in human basophils and was distinctly regulated by IL-2, independently of IL-3 and IgE. Immunofluorescence analysis of skin specimens from bullous pemphigoid and eczema revealed that infiltrating basophils in skin lesions widely express IL-5 and GM-CSF. Together, our findings reveal IL-2 as a novel regulator of human basophils to express IL-5 and GM-CSF in skin disorders. This adds a new layer to support the importance of basophils in skin disorders.

2018-10-01 | GSE74375 | GEO

Mus musculus breed:129S1/Sv-129X1/SvJ-C57BL/6J Itga11-/-

Project description:Differential gene expression in the skin of Aldara-induced psoriasiform dermatitis (AIPD) mouse model in Itga11 ko mice

| PRJNA869122 | ENA

NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon recognition in mitochondrial translation

Project description:Mitochondrial gene expression uses a non-universal genetic code in mammals. Besides reading the conventional AUG codon, mitochondrial (mt-)tRNAMet mediates incorporation of methionine on AUA and AUU codons during translation initiation and on AUA codons during elongation. We show that the RNA methyltransferase NSUN3 localises to mitochondria and interacts with mt-tRNAMet to methylate cytosine 34 (C34) at the wobble position. NSUN3 specifically recognises the anticodon stem loop (ASL) of the tRNA, explaining why a mutation that compromises ASL basepairing leads to disease. We further identify ALKBH1/ABH1 as the dioxygenase responsible for oxidising m5C34 of mt-tRNAMet to generate an f5C34 modification. In vitro codon recognition studies with mitochondrial translation factors reveal preferential utilization of m5C34 mt-tRNAMet in initiation. Depletion of either NSUN3 or ABH1 strongly affects mitochondrial translation in human cells, implying that modifications generated by both enzymes are necessary for mt-tRNAMet function. Together, our data reveal how modifications in mt-tRNAMet are generated by the sequential action of NSUN3 and ABH1, allowing the single mitochondrial tRNAMet to recognise the different codons encoding methionine. HEK293 cell lines expressing His-FLAG-tagged NSUN3 or the His-FLAG tag alone were crosslinked using UV or treated with 5-azacytidine and analysed by CRAC

2016-08-09 | E-GEOD-84664 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data