Pro-inflammatory activity of Cutibacterium acnes phylotype IA1 and extracellular vesicles: An in vitro study.

Acne is a chronic inflammatory skin condition that involves Cutibacterium acnes (C. acnes), which is classified into six main phylotypes (IA1, IA2, IB, IC, II and III). Acne development is associated with loss of C. acnes phylotype diversity, characterised by overgrowth of phylotype IA1 relative to other phylotypes. It was also shown that purified extracellular vesicles (EVs) secreted by C. acnes can induce an acne-like inflammatory response in skin models. We aimed to determine if the inflammatory profile of EVs secreted by C. acnes phylotype IA1 from an inflammatory acne lesion was different from C. acnes phylotype IA1 from normal skin, thus playing a direct role in the severity of inflammation. EVs were produced in vitro after culture of two clinical strains of C. acnes phylotype IA1, T5 from normal human skin and A47 from an inflammatory acne lesion, and then incubated with either human immortalised keratinocytes, HaCaT cells, or skin explants obtained from abdominoplasty. Subsequently, quantitative PCR (qPCR) was performed for human ß-defensin 2 (hBD2), cathelicidin (LL-37), interleukin (IL)-1ß, IL-6, IL-8, IL-17α and IL-36γ, and ELISA for IL-6, IL-8 and IL-17α. We found that EVs produced in vitro by C. acnes derived from inflammatory acne lesions significantly increased the pro-inflammatory cytokines and anti-microbial peptides at both transcriptional and protein levels compared with EVs derived from normal human skin. We show for the first time that C. acnes EVs from inflammatory acne play a crucial role in acne-associated inflammation in vitro and that C. acnes phylotype IA1 collected from inflammatory acne lesion and normal skin produce different EVs and inflammatory profiles in vitro.

Causal effects of skin microbiota on intervertebral disk degeneration, low back pain and sciatica: a two-sample Mendelian randomization study.

OBJECTIVE: The purpose of this study is to use two-sample Mendelian randomization (MR) to investigate the causal relationship between skin microbiota, especially Propionibacterium acnes, and intervertebral disc degeneration (IVDD), low back pain (LBP) and sciatica. METHODS: We conducted a two-sample MR using the aggregated data from the whole genome-wide association studies (GWAS). 150 skin microbiota were derived from the GWAS catalog and IVDD, LBP and sciatica were obtained from the IEU Open GWAS project. Inverse-variance weighted (IVW) was the primary research method, with MR-Egger and Weighted median as supplementary methods. Perform sensitivity analysis and reverse MR analysis on all MR results and use multivariate MR to adjust for confounding factors. RESULTS: MR revealed five skin microbiota associated with IVDD, four associated with LBP, and two with sciatica. Specifically, P.acnes in sebaceous skin environments were associated with reduced risk of IVDD; IVDD was found to increase the abundance of P.acnes in moist skin. Furthermore, ASV010 [Staphylococcus (unc.)] from dry skin was a risk factor for LBP and sciatica; ASV045 [Acinetobacter (unc.)] from dry skin and Genus Rothia from dry skin exhibited potential protective effects against LBP; ASV065 [Finegoldia (unc.)] from dry skin was a protective factor for IVDD and LBP. ASV054 [Enhydrobacter (unc.)] from moist skin, Genus Bacteroides from dry skin and Genus Kocuria from dry skin were identified as being associated with an increased risk of IVDD. Genus Streptococcus from moist skin was considered to be associated with an increased risk of sciatica. CONCLUSIONS: This study identified a potential causal relationship between skin microbiota and IVDD, LBP, and sciatica. No evidence suggests skin-derived P.acnes is a risk factor for IVDD, LBP and sciatica. At the same time, IVDD can potentially cause an increase in P.acnes abundance, which supports the contamination theory.

An integrated network pharmacology and molecular docking approach to reveal the role of Arctigenin against Cutibacterium acnes-induced skin inflammation by targeting the CYP19A1.

Acne caused by inflammation of hair follicles and sebaceous glands is a common chronic skin disease. Arctigenin (ATG) is an extract of Arctium lappa L., which has significant anti-inflammatory effects. However, the effect and mechanism of ATG in cutaneous inflammation mediated by Cutibacterium acnes (C. acnes) has not been fully evaluated. The purpose of this study was to explore the effect and potential mechanism of ATG in the treatment of acne through network pharmacology and experimental confirmation. An acne model was established by injected live C. acnes into living mice and treated with ATG. Our data showed that ATG effectively improved acne induced by live C. acnes, which was confirmed by determining ear swelling rate, estradiol concentration and hematoxylin and eosin (H&E) staining. In addition, ATG inhibited the NLRP3 inflammasome signaling pathway in mice ear tissues and reduced the secretion of pro-inflammatory cytokines IL-1ß to relieve inflammation. The results of network pharmacology and molecular docking confirmed that ATG can regulate 17ß-Estradiol (E2) levels through targeted to CYP19A1, and finally inhibited skin inflammation. Taken together, our results confirmed that ATG regulated E2 secretion by targeting CYP19A1, thereby inhibiting the NLRP3 inflammasome signaling pathway and improving inflammation levels in acne mice. This study provides a basis for the feasibility of ATG in treating acne in clinical practice.

A dermocosmetic product containing the sap of oat plantlets and Garcinia mangostana extract improves the clinical signs of acne.

BACKGROUND: Acne vulgaris is a common chronic inflammatory disorder of the pilosebaceous unit, characterized by papules, pustules and/or nodules manifesting primarily on the face and/or upper back that can leave scars, post-inflammatory hyperpigmentation (PIH) and erythema (PIE). OBJECTIVE: To evaluate the anti-inflammatory properties of a protein-free sap extruded from Rhealba® oat plantlets and a Garcinia mangostana extract on Cutibacterium acnes-induced inflammation in vitro and assess the tolerability and efficacy of a dermocosmetic product containing these actives in subjects with mild-to-moderate acne. METHODS: Monocyte-derived dendritic cells (Mo-DCs) from acne patients were stimulated with a planktonic culture of C. acnes and cytokine production was evaluated before and after addition of the test extracts by RT-PCR and ELISA. The clinical study was conducted in subjects with mild-to-moderate acne who applied the product to their face and upper back twice-daily for 2 months. RESULTS: Cutibacterium acnes-induced IL-6, IL-12p40, IL-10 and TNFα synthesis was reduced by the addition of the Garcinia mangostana extract and oat sap in vitro. The clinical study included 54 subjects. The 2-month, twice-daily application of the test product to the whole face and acne-affected areas on the upper back was well tolerated. It led to significant decreases in the number of retentional (-21% for 69% of subjects at D57) and inflammatory (-35% for 79% of subjects at D57) acne lesions, as well as a decrease in Global Acne Evaluation severity scores (2.5 at D1, 2.2 at D29 and 2.1 at D57). The dermatologist also rated the product as effective or very effective in most subjects with PIE (82%; n = 33/40) and PIH (70%; n = 8/11) at D57. CONCLUSION: The actives demonstrated anti-inflammatory effects in vitro, and the dermocosmetic product showed good clinical efficacy and tolerability in subjects with mild-to-moderate acne, supporting the use of this product in acne management.

Syringic acid suppresses Cutibacterium acnes-induced inflammation in human keratinocytes via regulating the NLRP3/caspase-1/IL-1ß signaling axis by activating PPARγ/Nrf2-antioxidant pathway.

BACKGROUND: Our previous studies have demonstrated a strong relationship betweenCutibacterium acnes(C. acnes), oxidative stress, and acne inflammation. Syringic acid (SA) is a plant widely used for its antimicrobial, anti-inflammatory, and antioxidant activities, but lacking data on acne. This study aims to investigate the effect and mechanism of SA on acne inflammation induced by C. acnes in vitro and in vivo. METHODS: After using the SA to expose HaCaT keratinocytes, we reevaluated the effect of the SA on cell viability, cell apoptosis, ROS, CAT, SOD, and other inflammatory variables in the heat-killed C. acnes-treated HaCaT cells. Next, to induce mice with acne inflammation, ICR mice were given an intradermal injection of live C. acnes into their right ears. The effect of SA on this inflammation was then examined. Moreover, we explored the mechanism of SA on PPARγ/Nrf2 and NLRP3/caspase-1/IL-1ß pathways by ELISA, immunofluorescence microscopy, and western blot assay. RESULTS: Heat-killed C. acnes triggered remarkable cell apoptosis, ROS production, interleukin (IL)-1ß, IL-18, IL-6, and TNF-α release, reduced SOD and CAT activity, and upregulated the expression of proteins in HaCaT cells, including up-regulating IL-1ß, PPARγ, Nrf2, HO-1, NQO1, NLRP3, and caspase-1, whereas SA inhibited these effects by partially impairing PPARγ activation. In addition, PPARγ silencing decreased C. acnes-induced IL-1ß secretion and the production of intracellular ROS, down-regulating the expression of Nrf2. Nrf2 activator (SFN) enhanced anti-inflammatory activity through antioxidant mechanisms, boosting intracellular ROS production, reducing SOD and CAT activity, and promoting the increase in ROS, HO-1, NQO1, and IL-1ß levels, while PPARγ inhibitor (GW662) effectively inhibited this effect in heat-killed C. acnes-treated cells. Finally, SA also exhibited notable improvements in ear redness, swelling, and the expression of PPARγ, NLRP3, and IL-1ß in vivo. CONCLUSIONS: SA inhibited C. acnes-induced inflammation via regulating the NLRP3/caspase-1/IL-1ß signaling axis by activating the PPARγ/Nrf2-antioxidant pathway, suggesting a new treatment possibility for acne vulgaris.

Cutibacterium acnes induces acne-like lesions in hairless mice models - A comparative study.

Acne vulgaris, a chronic inflammatory skin disease with a high prevalence worldwide, necessitates reliable preclinical models for both understanding its pathogenesis and evaluating potential anti-acne therapies. This study aims to establish a robust mouse model using intracutaneous injection of Cutibacterium acnes bacterial suspension. Three hairless mouse strains (SKH-hr1, SKH-hr2 brown, and SKH-hr2 + ApoE) were systematically compared to ascertain the stains most closely resembling acne in humans. Various assessments, including photo documentation, biophysical evaluation, blood analysis, and histopathology, were conducted. Despite all strains exhibiting acne-like lesions, SKH-hr1 mice emerged as the most suitable model, demonstrating the most satisfactory results across multiple criteria. This research underscores the significance of employing hairless mice strains as models in acne studies to enhance and facilitate the development of effective therapeutic interventions.

Bioadhesive Polymeric Films Containing Rhamnolipids, An Innovative Antimicrobial Topical Formulation.

Acne affects most of the world's population, causing an impact on the self-esteem of adolescents and young adults. One of the causes is the presence of the bacteria Cutibacterium acnes which are part of the natural microbiota of the skin. Topical treatments consist of anti-inflammatory and antibiotics, which could select resistant strains. Alternatives to the antibiotic are biocomposites that have antimicrobial activity like biosurfactants which are produced by bacteria. An innovative way of applying these compounds is bioadhesive polymeric films that adhere to the skin and release the active principle topically. Rhamnolipids have great potential to be used in the treatment of acne because they present antimicrobial activity against C. acnes in low and safe concentrations (MIC of 15.62 µg/mL, CBM of 31.25 µg/mL and CC50 of 181.93 µg/mL). Four films with different rhamnolipids concentrations (0.0; 0.1; 0.2; and 0.3%, w/w) were obtained as to visual appearance, mass variation, thickness, density, solubility, pH, water vapor transmission, mechanical properties (folding endurance, bioadhesion strength, tensile strength, elongation at break and Young's modulus), scanning electron microscopy and infrared. The results show that these formulations had a homogeneous appearance; elastic mechanical properties; pH similar to human skin and bioadhesive. The polymeric films containing rhamnolipids were effective against C. acnes, in the in vitro test, at the three concentrations tested, the film with the highest concentration (0.3%, w/w) being the most promising for presenting the highest antimicrobial activity. Thus, the polymeric film containing rhamnolipids has the potential to be used in the treatment of acne.

Antibacterial toner exhibits bactericidal effect against Cutibacterium acnes via keratin and sebum plug penetration.

Cutibacterium acnes is an opportunistic pathogen recognized as a contributing factor to acne vulgaris. The accumulation of keratin and sebum plugs in hair follicles facilitates C. acnes proliferation, leading to inflammatory acne. Although numerous antimicrobial cosmetic products for acne-prone skin are available, their efficacy is commonly evaluated against planktonic cells of C. acnes. Limited research has assessed the antimicrobial effects on microorganisms within keratin and sebum plugs. This study investigates whether an antibacterial toner can penetrate keratin and sebum plugs, exhibiting bactericidal effects against C. acnes. Scanning electron microscopy and next-generation sequencing analysis of the keratin and sebum plug suggest that C. acnes proliferate within the plug, predominantly in a biofilm-like morphology. To clarify the potential bactericidal effect of the antibacterial toner against C. acnes inside keratin and sebum plugs, we immersed the plugs in the toner, stained them with LIVE/DEAD BacLight Bacterial Viability Kit to visualize microorganism viability, and observed them using confocal laser scanning microscopy. Results indicate that most microorganisms in the plugs were killed by the antibacterial toner. To quantitatively evaluate the bactericidal efficacy of the toner against C. acnes within keratin and sebum, we immersed an artificial plug with inoculated C. acnes type strain and an isolate collected from acne-prone skin into the toner and obtained viable cell counts. The number of the type strain and the isolate inside the artificial plug decreased by over 2.2 log and 1.2 log, respectively, showing that the antibacterial toner exhibits bactericidal effects against C. acnes via keratin and sebum plug penetration.

Octahydroindolizine alkaloid Homocrepidine A from Dendrobium crepidatum attenuate P. acnes-induced inflammatory in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium crepidatum Lindl. ex Paxton is a perennial epiphyte of Dendrobium genus, distributed in southern China, and utilized as the traditional Chinese medicine "Shihu" in Yunnan Province. Due to its heat-clearing and detoxicating properties, it is formulated as the "XiaoCuoWan" as recorded in the China Pharmacopoeia, and specially used to treat chronic skin inflammatory diseases, such as acne. AIM OF THE STUDY: This research aimed to estimate impact of the octahydroindoline alkaloid Homocrepidine A (HCA), isolated from D. crepidatum, on acne inflammation using both human THP-1 cells and mouse models. Furthermore, the potential anti-inflammatory mechanism of HCA has been analyzed through molecular biology methods and computer simulation. MATERIALS AND METHODS: THP-1 cells and mouse models induced by live Propionibacterium acnes (P. acnes) were employed to evaluate the anti-inflammatory properties of crude extract of D. crepidatum (DCE) and HCA. ELISA was utilized to detect the release of inflammatory cytokines in both cellular and murine ear tissues. RNAseq was used to screen the pathways associated with HCA-mediated inflammatory inhibition, while Western blot, RT-qPCR, and immunofluorescence were utilized to detect the expression of relevant proteins. Additionally, molecular docking simulations and cellular thermal shift assays were employed to confirm the target of HCA. RESULTS: Our research shows that DCE and HCA can effectively alleviate acne inflammation. HCA inhibits TLR2 expression by interacting with amino acid residues in the TIR domain of hTLR2, including Pro-681, Asn-688, Trp-684, and Ile-685. Moreover, HCA disrupts inflammatory signal transduction mediated by MAPK and NF-κB pathways through MyD88-dependent pathway. Additionally, HCA treatment facilitates Nrf2 nuclear translocation and upregulates HO-1 expression, thereby inhibiting NLRP3 inflammasomes activation. In vivo experiments further revealed that HCA markedly attenuated erythema and swelling caused by P. acnes in mice ears, while also decreasing the expression of pro-inflammatory cytokines IL-1ß and IL-8. CONCLUSIONS: Our research highlights the protective effects of D. crepidatum and its bioactive compound HCA against acne inflammation, marking the first exploration of its potential in this context. The discoveries indicate that HCA treatment may represent a promising functional approach for acne therapy.

Carbon source competition within the wound microenvironment can significantly influence infection progression.

It is becoming increasingly apparent that commensal skin bacteria have an important role in wound healing and infection progression. However, the precise mechanisms underpinning many of these probiotic interactions remain to be fully uncovered. In this work, we demonstrate that the common skin commensal Cutibacterium acnes can limit the pathogenicity of the prevalent wound pathogen Pseudomonas aeruginosa in vivo. We show that this impact on pathogenicity is independent of any effect on growth, but occurs through a significant downregulation of the Type Three Secretion System (T3SS), the primary toxin secretion system utilised by P. aeruginosa in eukaryotic infection. We also show a downregulation in glucose acquisition systems, a known regulator of the T3SS, suggesting that glucose availability in a wound can influence infection progression. C. acnes is well known as a glucose fermenting organism, and we demonstrate that topically supplementing a wound with glucose reverses the probiotic effects of C. acnes. This suggests that introducing carbon source competition within the wound microenvironment may be an effective way to prevent or limit wound infection.

Antibacterial Properties of Peptide and Protein Fractions from Cornu aspersum Mucus.

The discovery and investigation of new natural compounds with antimicrobial activity are new potential strategies to reduce the spread of antimicrobial resistance. The presented study reveals, for the first time, the promising antibacterial potential of two fractions from Cornu aspersum mucus with an MW < 20 kDa and an MW > 20 kDa against five bacterial pathogens-Bacillus cereus 1085, Propionibacterium acnes 1897, Salmonella enterica 8691, Enterococcus faecalis 3915, and Enterococcus faecium 8754. Using de novo sequencing, 16 novel peptides with potential antibacterial activity were identified in a fraction with an MW < 20 kDa. Some bioactive compounds in a mucus fraction with an MW > 20 kDa were determined via a proteomic analysis on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and bioinformatics. High homology with proteins and glycoproteins was found, with potential antibacterial activity in mucus proteins named aspernin, hemocyanins, H-lectins, and L-amino acid oxidase-like protein, as well as mucins (mucin-5AC, mucin-5B, mucin-2, and mucin-17). We hypothesize that the synergy between the bioactive components determined in the composition of the fraction > 20 kDa are responsible for the high antibacterial activity against the tested pathogens in concentrations between 32 and 128 µg/mL, which is comparable to vancomycin, but without cytotoxic effects on model eukaryotic cells of Saccharomyces cerevisiae. Additionally, a positive effect, by reducing the levels of intracellular oxidative damage and increasing antioxidant capacity, on S. cerevisiae cells was found for both mucus extract fractions of C. aspersum. These findings may serve as a basis for further studies to develop a new antibacterial agent preventing the development of antibiotic resistance.

Multi-omics signatures reveal genomic and functional heterogeneity of Cutibacterium acnes in normal and diseased skin.

Cutibacterium acnes is the most abundant bacterium of the human skin microbiome since adolescence, participating in both skin homeostasis and diseases. Here, we demonstrate individual and niche heterogeneity of C. acnes from 1,234 isolate genomes. Skin disease (atopic dermatitis and acne) and body site shape genomic differences of C. acnes, stemming from horizontal gene transfer and selection pressure. C. acnes harbors characteristic metabolic functions, fewer antibiotic resistance genes and virulence factors, and a more stable genome compared with Staphylococcus epidermidis. Integrated genome, transcriptome, and metabolome analysis at the strain level unveils the functional characteristics of C. acnes. Consistent with the transcriptome signature, C. acnes in a sebum-rich environment induces toxic and pro-inflammatory effects on keratinocytes. L-carnosine, an anti-oxidative stress metabolite, is up-regulated in the C. acnes metabolome from atopic dermatitis and attenuates skin inflammation. Collectively, our study reveals the joint impact of genes and the microenvironment on C. acnes function.

Mapping the evolution of acne research based on 100 top-cited articles: A bibliometric analysis of trends and hotspots from 2014 to 2023.

BACKGROUND: Acne is a prevalent inflammatory condition of the pilosebaceous unit, which seriously affects the appearance and mental health of patients. Bibliometrics is the statistical analysis of academic literature in a certain field. We aimed to characterize the 100 most cited articles on acne from a bibliometric perspective, as well as explore the frontier hotspots and trends of acne. METHODS: A search was conducted on the Web of Science database on August 8, 2023. we employed the terms "acne," "acne Vulgaris," and "common acne" in our search. The top 100 articles with the most citations throughout the time frame of 2014 to 2023 were discovered and assessed. The visualization study was carried out using bibliometric tools such as CiteSpace 6.2.R4, VOSviewer 1.6.18, and MapChart. RESULTS: The top 100 most cited articles were published between 2014 and 2021, originated from a diverse range of 48 countries, with a predominant focus on the United States of America (USA) and Germany. The top 100 papers were cited between 50 and 712 times. Dreno B, from Nantes University, was the most frequently nominated author. With 12 papers, the Journal of the European Academy of Dermatology and Venereology contributed the most to the top 100 list. Alongside the term "acne", the following terms or phrases were observed frequency in the top 100 articles, Cutibacterium acnes, sebaceous, western diet, antibiotic resistance, staphylococcus-epidermidis, insulinlike growth factor 1, benzoyl peroxide, and polyunsaturated fatty acids. Alongside the term "acne", terms or phrases such as Cutibacterium acnes, sebaceous, western diet, antibiotic resistance, staphylococcus-epidermidis, insulinlike growth factor 1, benzoyl peroxide, and polyunsaturated fatty acids, etc also have a high frequency in the top 100 articles. CONCLUSION: This analysis summarizes the shifting trends of acne research over the last decades. Research on acne is currently flourishing. The related pathogenesis and therapeutic strategies have been the focus of current research and developmental trends in future research.

Investigation into the Anti-Acne Effects of Castanea sativa Mill Leaf and Its Pure Ellagitannin Castalagin in HaCaT Cells Infected with Cutibacterium acnes.

Acne vulgaris is a prevalent skin disorder affecting many young individuals, marked by keratinization, inflammation, seborrhea, and colonization by Cutibacterium acnes (C. acnes). Ellagitannins, known for their antibacterial and anti-inflammatory properties, have not been widely studied for their anti-acne effects. Chestnut (Castanea sativa Mill., C. sativa), a rich ellagitannin source, including castalagin whose acne-related bioactivity was previously unexplored, was investigated in this study. The research assessed the effect of C. sativa leaf extract and castalagin on human keratinocytes (HaCaT) infected with C. acnes, finding that both inhibited IL-8 and IL-6 release at concentrations below 25 µg/mL. The action mechanism was linked to NF-κB inhibition, without AP-1 involvement. Furthermore, the extract displayed anti-biofilm properties and reduced CK-10 expression, indicating a potential role in mitigating inflammation, bacterial colonization, and keratosis. Castalagin's bioactivity mirrored the extract's effects, notably in IL-8 inhibition, NF-κB inhibition, and biofilm formation at low µM levels. Other polyphenols, such as flavonol glycosides identified via LC-MS, might also contribute to the extract's biological activities. This study is the first to explore ellagitannins' potential in treating acne, offering insights for developing chestnut-based anti-acne treatments pending future in vivo studies.

Cryopreserved bone flaps from decompressive craniectomies: a microbiological analysis.

PURPOSE: Surgical site infection (SSI) is a serious complication after cranioplasty. Due to the relatively frequent occurrence of post-cranioplasty SSI, the utility of autologous bone flap swab cultures surrounding cryopreservation as a reliable predictor has been the subject of an ongoing debate. This bicentric study aims to contribute to this topic by conducting an in-depth analysis of bone flaps obtained via decompressive craniectomies. This study had three major aims: assessments of 1) bacterial contamination of bone flaps after decompressive craniotomy, 2) impact of cryoconservation on contamination rates and 3) potential effectiveness of anti-infective treatment to reduce the germ load prior to cranioplasty. METHODS: Cryopreserved bone flaps from two centers were used. Microbiological cultivations of swabs prior to and after cryopreservation were taken and assessed for aerobic and anaerobic growth over a 14-day incubation period. Additionally, in a subset of bone flaps, swab testing was repeated after thorough rinsing with an anti-infectant (octenidine-phenoxyethanol) followed by saline. RESULTS: All 63 bone flaps (patients median age at surgery: 59 years) were obtained via decompressive craniectomies. Swabs done prior to cryopreservation revealed a 54% infection rate with Propionibacterium acnes being the most common microorganism in 65% of those cases. After thorough disinfection of the preserved bone flaps, all but one case showed no bacterial growth in swab testing. Furthermore, no relevant risk factors for bacterial contamination could be identified. CONCLUSION: This retrospective study showed the common presence of bacterial growth in cryopreserved bone flaps before and after freezing. Rinsing with octenidine-phenoxyethanol and saline effectively prevented bacterial growth in a notable percentage of cases, suggesting a potential strategy to reduce contamination. However, persistent bacterial growth in some cases underscores the need for further research to optimize antiseptic measures during autologous cranioplasty.

[Understanding New Regulatory Mechanism of TCR Signal Transduction].

Signal-transducing adaptor protein-2 (STAP-2) is a unique scaffold protein that regulates several immunological signaling pathways, including LIF/LIF receptor and LPS/TLR4 signals. STAP-2 is required for Fas/FasL-dependent T cell apoptosis and SDF-1α-induced T cell migration. Conversely, STAP-2 modulates integrin-mediated T cell adhesion, suggesting that STAP-2 is essential for several negative and positive T cell functions. However, whether STAP-2 is involved in T cell-antigen receptor (TCR)-mediated T cell activation is unknown. STAP-2 deficiency was recently reported to suppress TCR-mediated T cell activation by inhibiting LCK-mediated CD3ζ and ZAP-70 activation. Using STAP-2 deficient mice, it was demonstrated that STAP-2 is required for the pathogenesis of Propionibacterium acnes-induced granuloma formation and experimental autoimmune encephalomyelitis. Here, detailed functions of STAP-2 in TCR-mediated T cell activation, and how STAP-2 affects the pathogenesis of T cell-mediated inflammation and immune diseases, are reviewed.

Dissolving Hyaluronic Acid-Based Microneedles to Transdermally Deliver Eugenol Combined with Photothermal Therapy for Acne Vulgaris Treatment.

A microneedle transdermal drug delivery system simultaneously avoids systemic toxicity of oral administration and low efficiency of traditional transdermal administration, which is of great significance for acne vulgaris therapy. Herein, eugenol-loaded hyaluronic acid-based dissolving microneedles (E@P-EO-HA MNs) with antibacterial and anti-inflammatory activities are developed for acne vulgaris therapy via eugenol transdermal delivery integrated with photothermal therapy. E@P-EO-HA MNs are pyramid-shaped with a sharp tip and a hollow cavity structure, which possess sufficient mechanical strength to penetrate the stratum corneum of the skin and achieve transdermal delivery, in addition to excellent in vivo biocompatibility. Significantly, E@P-EO-HA MNs show effective photothermal therapy to destroy sebaceous glands and achieve antibacterial activity against deep-seated Propionibacterium acnes (P. acnes) under near-infrared-light irradiation. Moreover, cavity-loaded eugenol is released from rapidly dissolved microneedle bodies to play a sustained antibacterial and anti-inflammatory therapy on the P. acnes infectious wound. E@P-EO-HA MNs based on a synergistic therapeutic strategy combining photothermal therapy and eugenol transdermal administration can significantly alleviate inflammatory response and ultimately facilitate the repair of acne vulgaris. Overall, E@P-EO-HA MNs are expected to be clinically applied as a functional minimally invasive transdermal delivery strategy for superficial skin diseases therapy in skin tissue engineering.

Intradermal injection of Cutibacterium acnes and staphylococcus: A pustular acne-like murine model.

BACKGROUND: Skin 16S microbiome diversity analysis indicates that the Staphylococcus genus, especially Staphylococcus aureus (S. aureus), plays a crucial role in the inflammatory lesions of acne. However, current animal models for acne do not fully replicate human diseases, especially pustular acne, which limits the development of anti-acne medications. AIMS: The aim is to develop a mouse model for acne, establishing an animal model that more closely mimics the clinical presentation of pustular acne. This will provide a new research platform for screening anti-acne drugs and evaluating the efficacy of clinical anti-acne experimental treatments. METHODS: Building upon the existing combination of acne-associated Cutibacterium acnes (C. acnes) with artificial sebum, we will inject a mixture of S. aureus and C. acnes locally into the dermis in a 3:7 ratio. RESULTS: We found that the acne animal model with mixed bacterial infection better replicates the dynamic evolution process of human pustular acne. Compared to the infection with C. acnes alone, mixed bacterial infection resulted in pustules with a distinct yellowish appearance, resembling pustular acne morphology. The lesions exhibited redness, vascular dilation, and noticeable congestion, along with evident infiltration of inflammatory cells. This induced higher levels of inflammation, as indicated by a significant increase in the secretion of inflammatory factors such as IL-1ß and TNF-α. CONCLUSION: This model can reflect the clinical symptoms and development of human pustular acne, overcoming the limitations of animal models commonly used in basic research to study this situation. It provides support for foundational research and the development of new acne medications.

TRPV3 promotes sebocyte inflammation via transcriptional modulating TLR2 in acne.

Acne is a common chronic inflammatory disease of the pilosebaceous unit. Transient receptor potential vanilloid 3 (TRPV3) is an ion channel that is involved in inflammatory dermatosis development. However, the involvement of TRPV3 in acne-related inflammation remains unclear. Here, we used acne-like mice and human sebocytes to examine the role of TRPV3 in the development of acne. We found that TRPV3 expression increased in the skin lesions of Propionibacterium acnes (P. acnes)-injected acne-like mice and the facial sebaceous glands (SGs) of acne patients. TRPV3 promoted inflammatory cytokines and chemokines secretion in human sebocytes and led to neutrophil infiltration surrounding the SGs in acne lesions, further exacerbating sebaceous inflammation and participating in acne development. Mechanistically, TRPV3 enhanced TLR2 level by promoting transcriptional factor phosphorylated-FOS-like antigen-1 (p-FOSL1) expression and its binding to the TLR2 promoter, leading to TLR2 upregulation and downstream NF-κB signaling activation. Genetic or pharmacological inhibition of TRPV3 both alleviated acne-like skin inflammation in mice via the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebaceous inflammation and indicated its potential as an acne therapeutic target.