Project description:Neutrophils are key contributors to the pathogenesis of SLE. Using single-cell sequencing data from SLE skin lesions, we identified a subcluster of CXCL1+ fibroblasts primarily induced by IL-1β. To better understand the effects of CXCL1+ fibroblasts on neutrophils, we established a conditional culture model using culture supernatants from control and IL-1β-stimulated fibroblasts. Neutrophils were collected after 21 hours of conditional culture and subjected to RNA-seq. Our findings revealed that neutrophils exhibited a distinct pro-inflammatory phenotype, expressing higher levels of pro-inflammatory cytokines such as IL1B, TNFA, IL8, and OSM.
Project description:To gain a better understanding of the role of Interleukin-1β (IL-1β) in lung CD140a+ mesenchymal cells (fibroblasts) modulation, we performed RNA-seq to compare the transcriptomes of IL-1β-treated and control lung CD140a+ mesenchymal cells (fibroblasts).
Project description:Fibroblasts display significant heterogeneity and exhibit distinct gene expression profiles under different cytokine stimulations. We utilized RNA-seq to analyze the expression profile differences between control and IL-1β stimulated fibroblasts( n=3). Our analysis revealed 1756 differentially expressed genes between WT and Smyd1-KO hearts [adjusted P-value <0.05, |log2(fold change)| > 0.5]. Among these, 755 genes were upregulated, and 843 genes were downregulated in IL-1β stimulated human dermal fibroblasts. Notably, IL-1β stimulation can induce fibroblast differentiation into pro-inflammatory fibroblasts, characterized by the expression of neutrophil-related chemokines (CXCL1, CXCL2, CXCL3), ferroptosis-related genes (PTGS2, TNFAIP6), and pro-inflammatory cytokines (IL6). Our findings lay the groundwork for understanding the IL-1β-induced fibroblast expression of specific gene profiles.
Project description:Analysis of response to leptin and IL-1β in gingival fibroblasts at the gene expression level. The hypothesis tested in the present study was that leptin and IL-1β synergistically effect the phenotype of gingival fibroblasts. Results provide important information regarding the response of gingival fibroblasts to leptin and IL-1β, such as specific inflammatory genes that were up- or down-regulated.
Project description:Analysis of the effects of AVS023 and its active compounds (gallic acid and piperine) on human gene expression in primary human dermal fibroblasts induced by IL-1β. The results provided up- and down- regulated genes resulting from IL-1β and IL-1β plus with each test compound in primary human dermal fibroblasts
Project description:HOIL-1 deficient disease is a new early onset fatal autosomal recessive human disorder charaterized by chronic auto-inflammation, recurrent invasive bacterial infections and progressive muscular amylopectinosis. We studied the effect of TNF-α and IL-1β on transcriptional changes of primary fibroblasts from HOIL-1-, MYD88- and NEMO-deficient patients. Primary fibroblasts were obtained from HOIL-1, MYD88- and NEMO-deficient patients and healthy donors and stimulated with TNF-α or IL-1β for 2 and 6 hours. RNA were extracted and globin reduced. Labeled cRNA were hybridized to Illumina Human HT-12 Beadchips.
Project description:Neutrophil abscess formation is critical in innate immunity against many pathogens. Here, the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection. Gene expression analysis of S. aureus-infected skin revealed that induction of neutrophil recruitment genes was largely dependent upon IL-1beta/IL-1R activation. Unexpectedly, using IL 1beta reporter mice, neutrophils were identified as the primary source of IL-1beta at the site of infection. Furthermore, IL-1beta-producing neutrophils were necessary and sufficient for abscess formation and bacterial clearance. S. aureus-induced IL 1beta production by neutrophils required TLR2, NOD2, FPRs and the ASC/NLRP3 inflammasome. Taken together, IL-1beta and neutrophil abscess formation during an infection are functionally, spatially and temporally linked as a consequence of direct IL-1beta production by neutrophils. Lesional skin biopsies obtained from C57BL/6J WT mice or IL-1R-deficient mice at 4 hours post-infection with Staphylococcus aureus. Uninfected skin biopsies were also collected from WT and IL-1R-deficient mice.
Project description:To investigate the effects of IL-1β/IL-6/PGE2 on neutrophil modulation, we performed RNA-seq to compare IL-1β/IL-6/PGE2-treated neutrophils to vehicle-treated neutrophils.
Project description:The complex system by which the skin regulates immune responses to the external environment is unclear. Here, we investigated cell-cell interactions underlying cutaneous defense against S. aureus. Single-cell transcriptomics (scRNA-Seq) and unbiased network analysis revealed unexpected, dominant IL-17-mediated dermal reticular fibroblast-to-neutrophil communication. Multi-faceted in vitro omics studies demonstrated that IL-17 synergized with several factors including TNF⍺ to induce fibroblast NFKBIZ and chemokine secretion. Cultured fibroblasts drove robust neutrophil recruitment through NFKBIZ-dependent CXCR2 and CXCR4 ligands. Mice lacking IL-17R in fibroblasts (PdgfraΔIl17ra) were generated to determine the significance of fibroblast-neutrophil communication. PdgfraΔIl17ra mice exhibited drastically reduced skin neutrophilia in multiple disease models and reduced defense against S. aureus. These findings were translated to humans by comprehensive analysis of biopsies from psoriasis patients on and off anti-IL-17 treatment. Thus, dermal fibroblasts are critical for skin type 17 inflammation and represent a novel target for treatment of infection and inflammatory disease.