RNA-seq of primary human keratinocytes : Effects of IL-20 on gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE195538 | GEO | 2022/08/03
REPOSITORIES: GEO
Similar Datasets
Project description:In the present study, RNA-seq were performed To explore biological significance of IL-27 and BST2 in the neuro-cutaneous signaling network of chronic itch. mRNA profiles were generated by deep sequencing, in triplicate, using MGISEQ-2000. We found that both human keratinocytes and murine sensory neurons responded to IL-27 and BST2, resulting in enrichment of genes promoting itch and inflammation. IL-27-BST2 signaling pathway activation promotes cutaneous inflammation and itch, both leading into an aggravation of AD. This finding might help us to better understand the immune-neuro-modulatory mechanism in itch circuits
2024-03-05 | GSE188242 | GEO
Project description:In the present study, RNA-seq technique were performed To explore biological significance of MMP9 in the neuro-cutaneous signaling network of chronic itch. We used MMP-9-IN-1, a specific inhibitor of MMP9, or its vehicle to treat ACD model mice, and conducted high-throughput sequencing on ear tissue samples of mice. It was found that inhibition of MMP9 expression affected the expression of a variety of itching factors and skin inflammatory factors related to the skin pathology of chronic dermatitis. These changes may indicate that MMP9 is closely related to inflammation and pruritus. This finding might help us to better understand the immune-neuro-modulatory mechanism in itch circuits.
2024-02-13 | GSE232349 | GEO
Project description:In the present study, RNA-seq were performed To identify clinical relevance of PLAUR, a putative Serpin E1 receptor, in cutaneous itch signaling and crosstalk pathways with other critical itch modulators.mRNA profiles were generated by deep sequencing, in triplicate, using MGISEQ-2000. Our experiment showed Serpin E1-treatment further led to a marked upregulation of TLR2 transcript in mDRG neurons, along with enhanced transcription of cosignaling proteins belonging to pro-inflammatory signaling pathways including NF-κB signaling proteins. We next investigated the consequence of TLR2 activation in mTGNs using the TLR agonists, Pam3CSK4 (TLR1/2 agonist), FSL-1 (TLR2/6 agonist), or vehicle. Among these transcripts, TLR2 was found upregulated strongest by both TLR2 agonists suggesting a selfenhancing feedback loop of TLR2 activation.The PLAUR-TLR2 axis promotes cutaneous inflammation and itch, both feeding into an aggravation of AD. This finding might help us to better understand the skin-nerve communication in itch circuits.
2022-08-03 | GSE189333 | GEO
Project description:Allergic conjunctivitis is a chronic inflammatory disease that is characterized by severe itch in the conjunctiva; but how neuro-immune interactions shape the pathogenesis of severe itch remains unclear. We identified a subset of memory-type pathogenic Th2 cells that preferentially expressed Il1rl1-encoding ST2 and Calca-encoding calcitonin gene-related peptide (CGRP) in the inflammatory conjunctiva using a single-cell analysis. The IL-33-ST2 axis in memory Th2 cells controlled the axonal elongation of the peripheral sensory C-fiber and the induction of severe itch. Pharmacological blockade and genetic deletion of CGRP signaling in vivo attenuated scratching behavior. The analysis of giant papillae from patients with severe allergic conjunctivitis revealed ectopic lymphoid structure formation with the accumulation of IL-33-producing epithelial cells and CGRP-producing pathogenic CD4+ T cells accompanied by peripheral nerve elongation. Thus, the IL-33-ST2-CGRP axis directs severe itch with neuro-reconstruction in the inflammatory conjunctiva and is a potential therapeutic target for severe itch in allergic conjunctivitis.
2022-05-20 | GSE203217 | GEO
Project description:To test the hypothesis that defects in the termination of inflammatory signaling led to skin inflammation that results in the “Itchy” phenotype, we isolated RNA from the lesional skin of Itch-/- mice and from the skin of wild-type mice and performed genome-wide mRNA expression profiling by RNA sequencing. We ranked genes based on the fold change in their expression (increased or decreased) in Itch-/- skin relative to that in wild-type skin. The expression of several TNF–induced genes were increased in Itch-/- skin, including, IL-1?, IL-6, IL-11, IL-19, IL-1RL1, CCL4, CXCL3, CXCL2, CCL3, and CD14. mRNA profiles comparison between wild type (WT) skin and Itch-/- mice lesional skin
2015-03-04 | E-GEOD-65686 | biostudies-arrayexpress
Project description:Introduction Disruption of the epithelial barrier can induce eosinophilic esophagitis (EoE), a TH2-mediated food- and aeroallergen associated chronic inflammatory disease 1, 2. The expression of IL-20 subfamily cytokines, IL-19, IL-20 and IL-24, is increased in TH2-mediated diseases, yet their function in EoE is unknown. Methods Combining RNA-sequencing (RNA-seq) and proteome analysis, we have examined the effects of the IL-20 subfamily on esophageal epithelial cells using patient-derived organoids and an experimental EoE mouse model. Results When stimulated with IL-20 subfamily cytokines patient-derived esophageal organoids showed decreased expression of Filaggrin (FLG) and Filaggrin 2 (FLG2) responsible for epithelial cornification. In agreement, EoE patients with active inflammation showed elevated IL-20 subfamily cytokines and decreased FLG and FLG2 expression. Topical corticosteroid treatment in EoE patients restored filaggrin expression, while reducing IL-20 subfamily cytokines. Abolishment of IL-20 subfamily signalling in Il20R2-/- animals attenuated experimental EoE in an OVA-induced mouse model. In the esophageal keratinocyte cell line, KYSE-180, we identified IL-20 subfamily-induced STAT3 and MAPK (ERK1/2) pathway activation. However, Stat3fl/flKrt5cre mice with an epithelium specific deletion of Stat3 developed exacerbated experimental EoE with a pronounced decrease of Flg2. In line, combined stimulation of patient-derived esophageal organoids with IL-20 subfamily cytokines and pharmacological inhibition of STAT3 resulted in aggravated decrease of FLG and FLG2. In addition, pharmacological STAT3 inhibition resulted in reduced transepithelial electrical resistance (TEER) and increased macromolecular flux in patient-derived air liquid interface (ALI) cultures. Whereas, inhibition of the MAPK (ERK1/2) pathway hampered IL-20 subfamily induced TEER reduction and paracellular flux increment. Finally, MAPK (ERK1/2) inhibitor treatment reduced infiltrating CD45+ immune cells in the esophagus and alleviated experimental EoE in mice. Conclusion We discovered a novel regulatory function of the IL-20 subfamily for epithelial barrier integrity. Aberrant IL-20 subfamily signaling disturbs the epithelial barrier function, while abrogation of IL-20 subfamily and ERK1/2 signaling restores epithelial integrity and attenuates experimental EoE. Therefore, we propose that targeting the IL-20 subfamily pathway could present a novel therapeutic strategy for EoE treatment.
2023-05-10 | PXD031509 | Pride
Project description:Cutaneous afferent neurons express receptors for type 2 cytokines, including interleukins (IL)-4, IL-13, and IL-33. These neuronal cytokine receptors were found to be required in several murine models of itch. The objective of the present study was to determine if type 2 cytokine stimulation sensitizes sensory neurons to future itch stimuli in a fully human ex vivo system. Human dorsal root ganglia were isolated and dissociated to establish ex vivo cultures and subjected to 24 hours of type 2 cytokine exposure with either vehicle, IL-4, IL-13, IL-33, or IL-4 and IL-13 together. After 24 hours, cells were harvested and RNA extracted and sequenced to determine the transcriptomic effects of type 2 cytokine exposure.
2023-09-22 | GSE242488 | GEO
Project description:To test the hypothesis that defects in the termination of inflammatory signaling led to skin inflammation that results in the “Itchy” phenotype, we isolated RNA from the lesional skin of Itch-/- mice and from the skin of wild-type mice and performed genome-wide mRNA expression profiling by RNA sequencing. We ranked genes based on the fold change in their expression (increased or decreased) in Itch-/- skin relative to that in wild-type skin. The expression of several TNF–induced genes were increased in Itch-/- skin, including, IL-1β, IL-6, IL-11, IL-19, IL-1RL1, CCL4, CXCL3, CXCL2, CCL3, and CD14.
2015-03-04 | GSE65686 | GEO
Project description:In naïve individuals, sensory neurons directly detect and respond to allergens, leading both to the sensation of itch and the activation of local innate immune cells, which initiate the allergic immune response1,2. In the setting of chronic allergic inflammation, immune factors prime sensory neurons, causing pathologic itch3-7. While these bidirectional neuroimmune circuits drive responses to allergens, whether immune cells regulate the set-point for neuronal activation by allergens in the naïve state is unknown. Here we describe a T cell-IL-3 signaling axis that controls the allergen responsiveness of cutaneous sensory neurons. We define a poorly characterized epidermal T cell subset8, termed GD3 cells, that produces its hallmark cytokine IL-3 to promote allergic itch and the initiation of the allergic immune response. Mechanistically, IL-3 acts on Il3ra-expressing sensory neurons in a JAK2-dependent manner to lower their threshold for allergen activation without independently eliciting itch. This T cell-IL-3 signaling axis further acts via STAT5 to promote neuropeptide production and the initiation of allergic immunity. These results reveal an endogenous immune rheostat that sits upstream of and governs sensory neuronal responses to allergens upon first exposure. This pathway may explain individual differences in allergic susceptibility and opens novel therapeutic avenues for treating allergic diseases.
2024-06-11 | GSE223220 | GEO
Project description:To mount an anti-pathogen response, CD4 T cells must undergo rapid cell proliferation. However, poorly controlled expansion can result in diseases such as autoimmunity. One important regulator of T cell activity is the E3 ubiquitin ligase Itch. Itch deficient patients suffer from extensive autoinflammation. Similarly, Itch deficient mice exhibit inflammation characterized by high numbers of activated CD4 T cells. While the role of Itch in limiting CD4 T cell cytokine production has been extensively studied, it is less clear whether and how Itch regulates proliferation of these cells. We determined that Itch deficient CD4 T cells are hyperproliferative in vitro and in vivo, due to increased S phase entry. Whole cell proteomics analysis of Itch deficient primary mouse CD4 T cells revealed increased abundance of the -catenin co-activator WW domain binding protein 2 (WBP2). Furthermore, Itch deficient cells demonstrate increased WBP2 protein stability, and Itch and WBP2 interact in CD4 T cells. Knockdown of WBP2 in CD4 T cells caused reduced proliferation. Together, our data support that Itch attenuates CD4 T cell proliferation by promoting WBP2 degradation. This study identifies novel roles for Itch and WBP2 in regulating CD4 T cell proliferation, providing insight into how Itch may prevent inflammation.
2021-01-07 | PXD019272 | Pride