Antimicrobial production by perifollicular dermal preadipocytes is essential to the pathophysiology of acne
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ABSTRACT:
PROVIDER: PRJNA796789 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17598641_1.fastq.gz | Fastqsanger.gz | |||
| SRR17598641_2.fastq.gz | Fastqsanger.gz | |||
| SRR17598642_1.fastq.gz | Fastqsanger.gz | |||
| SRR17598642_2.fastq.gz | Fastqsanger.gz |
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Project description:Innate immune defense against deep tissue infection by Staphylococcus aureus is orchestrated by fibroblasts that become antimicrobial when triggered to differentiate into adipocytes. However, the role of this process in non-infectious human diseases is unknown. To investigate the potential role of adipogenesis by dermal fibroblasts in acne, a disorder triggered by Cutibacterium acnes (C. acnes), single-cell RNA-sequencing was performed on human acne lesions and mouse skin challenged by C. acnes. A transcriptome consistent with adipogenesis was observed within specific fibroblast subsets from human acne and mouse skin lesions infected with C. acnes. Perifollicular dermal preadipocytes in human acne and mouse skin lesions showed colocalization of PREF1, an early marker of adipogenesis, and cathelicidin (Camp), an antimicrobial peptide. This capacity of C. acnes to trigger production of cathelicidin in preadipocytes was dependent on TLR2. Treatment of wild-type mice with retinoic acid (RA) suppressed the capacity of C. acnes to form acne-like lesions, inhibited adipogenesis and enhanced cathelicidin expression in preadipocytes, but lesions were unresponsive in Camp-/- mice, despite the anti-adipogenic action of RA. Analysis of inflamed skin of acne patients after retinoid treatment also showed enhanced induction of cathelicidin, a previously unknown beneficial effect of retinoids in difficult-to-treat acne. Overall, these data provide evidence that adipogenic fibroblasts are a critical component of the pathogenesis of acne and represent a potential target for future therapy.
2022-01-16 | GSE193584 | GEO
Project description: Not available
| S-EPMC9885891 | biostudies-literature
Project description:The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. In an attempt to understand the specific genes involved in inflammatory acne, we performed gene expression profiling in acne patients. Skin biopsies were obtained from an inflammatory papule and from normal skin in six patients with acne. Biopsies were also taken from normal skin of six subjects without acne. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays comparing lesional to nonlesional skin in acne patients and comparing nonlesional skin from acne patients to skin from normal subjects. Within the acne patients, 211 genes are upregulated in lesional skin compared to nonlesional skin. A significant proportion of these genes are involved in pathways that regulate inflammation and extracellular matrix remodeling, and they include matrix metalloproteinases 1 and 3, IL-8, human beta-defensin 4, and granzyme B. These data indicate a prominent role of matrix metalloproteinases, inflammatory cytokines, and antimicrobial peptides in acne lesions. These studies are the first describing the comprehensive changes in gene expression in inflammatory acne lesions and are valuable in identifying potential therapeutic targets in inflammatory acne. Experiment Overall Design: total 18 chips. 6 for acne lesion samples, 6 for normal skin samples, 6 for non-acne patient normal skin samples
2008-06-14 | E-GEOD-6475 | biostudies-arrayexpress
Project description:The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. In an attempt to understand the specific genes involved in inflammatory acne, we performed gene expression profiling in acne patients. Skin biopsies were obtained from an inflammatory papule and from normal skin in six patients with acne. Biopsies were also taken from normal skin of six subjects without acne. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays comparing lesional to nonlesional skin in acne patients and comparing nonlesional skin from acne patients to skin from normal subjects. Within the acne patients, 211 genes are upregulated in lesional skin compared to nonlesional skin. A significant proportion of these genes are involved in pathways that regulate inflammation and extracellular matrix remodeling, and they include matrix metalloproteinases 1 and 3, IL-8, human beta-defensin 4, and granzyme B. These data indicate a prominent role of matrix metalloproteinases, inflammatory cytokines, and antimicrobial peptides in acne lesions. These studies are the first describing the comprehensive changes in gene expression in inflammatory acne lesions and are valuable in identifying potential therapeutic targets in inflammatory acne. Keywords: acne lesion, normal skin
2006-12-12 | GSE6475 | GEO
Project description:The mechanisms of inflammation in acne are not well understood. This study performed in two separate patient populations focused on the activation of adaptive and innate immunity in early inflamed acne. Biopsies were collected from lesional and non-lesional skin of acne patients. Psoriasis patients and healthy volunteers were included in the study for comparison (not included in the records). Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed with real-time qPCR (RT-PCR) in two separate patient populations. Cytokines involved in Th17 lineage differentiation (IL-1beta, IL-6, TGF-beta; IL23p19) were remarkably induced at the RNA level. In addition, pro-inflammatory cytokines (IL-8, TNF-α), Th1 markers (IL12p40, CXCR3, T-bet, IFN-gamma), T regulatory cell markers (Foxp3, IL-10, TGF-β) and antimicrobial peptides (S100A7, S100A9, LNC2, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway may play a pivotal role in the disease process, offering new targets of therapy. Total of 24 chips. 12 patients : 2 biospies per patient: 1 lesional and 1 non lesional.
2014-09-25 | E-GEOD-53795 | biostudies-arrayexpress
Project description:Background: Possible outcomes of acne lesions are atrophic scars which may cause serious physical and psychological distress. Current treatments of post-acne scarring remain difficult and often require invasive procedures. Pathophysiological studies on acne scaring investigated only the first week of papule life. Objectives: Study the pathophysiology of atrophic acne scar formation to identify molecular and cellular pathways that can lead to new therapies for the prevention of acne scarring. Methods: Large-scale gene expression profiling of uninvolved acne skin and acne papules of 48 hours and 3 weeks of age, respectively, of both, scar-prone (SP) and non-scar-prone (NSP) patients was performed. Immunohistochemistry techniques were applied to confirm transcriptomics results on the protein and cellular level. Results: Gene expression and immunohistochemistry analyses showed a very similar immune response in 48 hours-old papules in SP and NSP populations characterized by elevated numbers of T cells, neutrophils and macrophages. However, only in SP patients the immune response persisted in 3 week-old papules, and was characterized by an important infiltrate of B cells. Transient down-modulation of genes related to lipid metabolism was observed in 48 hours-old papules in NSP patients, followed by normalization of gene expression levels after 3 weeks. In contrast, in SP patients a drastic reduction of lipid metabolizing enzymes was observed in 3 week-old papules, suggesting irreversible modifications. The affected lipid metabolism genes were found preferentially expressed in human sebaceous glands, pointing to a destruction of sebaceous gland structures after 3 weeks of inflammatory remodelling in SP acne patients.
2018-04-30 | GSE108110 | GEO
Project description:Cutibacterium acnes (C. acnes) is a ubiquitous skin commensal bacterium that is generally well tolerated by the immune system. Different strain-types of C. acnes have been reported to be enriched on patients with acne. To understand if these strain-types contribute to skin inflammation, we generated a library of over 200 C. acnes isolates from skin swabs of healthy and acne subjects and assessed their strain-level identity and inflammatory potential. Phylotype II K-type strains were more frequent on healthy and acne non-lesional skin compared to lesional. Phylotype IA-1 C-type strains were dominant on acne lesional skin but absent from healthy. Measurement of host cytokine responses from C. acnes supernatant revealed neither strain-type nor skin-type association predicted inflammatory potential. However, differential proinflammatory responses were induced from identical strain-types, but these differences were not attributable to protease, short chain fatty acid or porphyrin production. Instead, whole genome sequencing revealed the presence of a linear plasmid in high inflammatory strain-types. Intradermal injection of C. acnes in mouse skin revealed a plasmid-associated inflammatory response in dermal fibroblasts, revealed by single-cell RNA sequencing. We conclude that C. acnes strain-type is not sufficient to predict inflammation but other virulence factors including a plasmid may contribute to disease.
2023-08-18 | GSE211279 | GEO
Project description:Dermal white adipose tissue (dWAT) is highly plastic and pivotal in host defense; however, its role in controlling neutrophil function remains unstudied. Here we found that Imiquimod-induced psoriatic skin inflammation prompted a dermal adipogenesis response, with preadipocyte expansion followed by differentiation into adipocytes. By single-cell RNAseq of the imiquimod skin samples, we found that dWAT was the primary site for initial neutrophil influx and activation, facilitated by interactions between neutrophils and preadipocytes via the IL1β-IL1R and CXCL1-CXCR2 pathways. IL1β-activated preadipocytes secreted CXCL1 and SAA3 to boost neutrophilic inflammation. Prolonged inflammation in preadipocytes led to their differentiation into early adipocytes, secreting anti-inflammatory lipids to resolve neutrophilic inflammation and restore homeostasis.
2025-07-18 | GSE238086 | GEO
Project description:The mechanisms of inflammation in acne are not well understood. This study performed in two separate patient populations focused on the activation of adaptive and innate immunity in early inflamed acne. Biopsies were collected from lesional and non-lesional skin of acne patients. Psoriasis patients and healthy volunteers were included in the study for comparison (not included in the records). Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed with real-time qPCR (RT-PCR) in two separate patient populations. Cytokines involved in Th17 lineage differentiation (IL-1beta, IL-6, TGF-beta; IL23p19) were remarkably induced at the RNA level. In addition, pro-inflammatory cytokines (IL-8, TNF-α), Th1 markers (IL12p40, CXCR3, T-bet, IFN-gamma), T regulatory cell markers (Foxp3, IL-10, TGF-β) and antimicrobial peptides (S100A7, S100A9, LNC2, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway may play a pivotal role in the disease process, offering new targets of therapy.
2014-09-25 | GSE53795 | GEO