Tissue expression of IL‐17A and FOXP3 in acne vulgaris patients

Shou

et al. 2021

Preprint

Background Acne vulgaris is a common inflammatory condition of skin. However, the landscape of immune infiltration in acne has not been entirely described. Objectives This study used a bioinformatics approach to investigate the inflammatory acne-related key biomarkers and signaling pathways, and immune infiltration in the acne lesion. Methods Two microarray datasets (GSE108110 and GSE53795) were downloaded from Gene Expression Omnibus. We used “limma” package from R software to identify the differentially expressed genes (DEGs) and perform the functional enrichment analyses. Then we built a protein-protein interaction network (PPI), performed the hub genes’ identification through STRING and Cytoscape. We applied the CIBERSORT algorithm to describe the immune infiltration in acne, and explored the correlation between biomarkers and immune infiltration. In the end, our findings in the study were verified by analyzing microarray dataset GSE6475. Results The differentially expressed genes (DEGs) including 292 upregulated genes and 150 downregulated genes in acne compared with non-lesional skin. The hub genes FPR1, C3AR1, CXCL1, CXCL8, FPR2, C3, CCR7, ITGB2 and pivotal pathways JAK-STAT signaling pathway, Toll-like receptor and NOD-like receptor signaling pathway were the most significantly associated with raising neutrophils, monocytes, activated mast cells, as well as reducing resting mast cells and Tregs. Conclusions Our study provides new insights into the pathogenesis and the targets which might be immunomodulatory potential for acne.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elucidating the Key Biomarkers and Immune Infiltration in Acne by Integrated Bioinformatics Analysis

Shou

et al. 2021

Preprint

“…Identified by the transcription factor FOXP3, these cells were detected in acne-affected individuals in their epidermis and in papillary dermis. Nevertheless, these cells do not appear to be associated with IL-17-producing cells, which might suggest a deficit in Treg function in acne vulgaris to control inflammatory events ( Farag et al, 2020 ).…”

Section: Inflammatory Response In Acnementioning

confidence: 99%

The immunomodulatory potential of phage therapy to treat acne: a review on bacterial lysis and immunomodulation

Farfán

González

Vives

2022

PeerJ

Background Characterized by an inflammatory pathogenesis, acne is the most common skin disorder worldwide. Altered sebum production, abnormal proliferation of keratinocytes, and microbiota dysbiosis represented by disbalance in Cutibacterium acnes population structure, have a synergic effect on inflammation of acne-compromised skin. Although the role of C. acnes as a single factor in acne development is still under debate, it is known that skin and skin-resident immune cells recognize this bacterium and produce inflammatory markers as a result. Control of the inflammatory response is frequently the target for acne treatment, using diverse chemical or physical agents including antibiotics. However, some of these treatments have side effects that compromise patient adherence and drug safety and in the case of antibiotics, it has been reported C. acnes resistance to these molecules. Phage therapy is an alternative to treat antibiotic-resistant bacterial strains and have been recently proposed as an immunomodulatory therapy. Here, we explore this perspective about phage therapy for acne, considering the potential immunomodulatory role of phages. Methodology Literature review was performed using four different databases (Europe PubMed Central-ePMC, Google Scholar, PubMed, and ScienceDirect). Articles were ordered and selected according to their year of publication, number of citations, and quartile of the publishing journal. Results The use of lytic bacteriophages to control bacterial infections has proven its promising results, and anti-inflammatory effects have been found for some bacteriophages and phage therapy. These effects can be related to bacterial elimination or direct interaction with immune cells that result in the regulation of pro-inflammatory cytokines. Studies on C. acnes bacteriophages have investigated their lytic activity, genomic structure, and stability on different matrices. However, studies exploring the potential of immunomodulation of these bacteriophages are still scarce. Conclusions C. acnes bacteriophages, as well as other phages, may have direct immunomodulatory effects that are yet to be fully elucidated. To our knowledge, to the date that this review was written, there are only two studies that investigate anti-inflammatory properties for C. acnes bacteriophages. In those studies, it has been evidenced reduction of pro-inflammatory response to C. acnes inoculation in mice after bacteriophage application. Nevertheless, these studies were conducted in mice, and the interaction with the immune response was not described. Phage therapy to treat acne can be a suitable therapeutic alternative to C. acnes control, which in turn can aid to restore the skin’s balance of microbiota. By controlling C. acnes colonization, C. acnes bacteriophages can reduce inflammatory reactions triggered by this bacterium.

“…Proinflammatory IL-17-generating cells and anti-inflammatory FOXP3 + Treg cells are the main factors for CD4 + T cells to play a crucial role in inflammatory diseases. In acne vulgaris, the expression levels of IL-17 and FOXP3 are increased in epidermal keratinocytes and lymphocytes (58). Cutibacterium acnes can induce the activation of IL-17, with one study finding that the expression of serum IL-17 was increased in patients with acne vulgaris scarring compared to those without (59).…”

Section: Progress Of Research In Immunological Pathogenesis In Acne V...mentioning

confidence: 99%

“…IL-17A plays an important role in acne vulgaris in a paracrine manner involving interaction between dermal lymphocytes and epidermal keratinocytes (60). IL-17, TNF-α, and IL-1 play synergistic roles in acne vulgaris by inducing the production of several metalloproteinases (58). Platelets may play a role in adaptive immunity in acne vulgaris by up-regulating lymphocytes (61).…”

Section: Progress Of Research In Immunological Pathogenesis In Acne V...mentioning

confidence: 99%

A narrative review of research progress on the role of NLRP3 inflammasome in acne vulgaris

Zhu¹,

Wang²,

Bu³

et al. 2022

Ann Transl Med

Background and Objective: Acne vulgaris is a common skin disease around the world which affects the appearance of patients, as well as their physical and mental health. Cutibacterium acnes plays a vital role in the occurrence and development of acne vulgaris. Pattern recognition receptors (PRRs) are the first line of defense against external pathogens. The nucleotide oligomerization domain (NOD)-like receptor family pyrin containing 3 (NLRP3) inflammasome has recently been shown to contribute to the pathogenesis of acne vulgaris. The purpose of this review is to clarify the underlying mechanisms of NLRP3 inflammasome in the pathogenesis of acne vulgaris, and its potential as a therapeutic target for the condition.Methods: The PubMed database was searched for relevant articles published in English between January 2003 to December 2021 using keywords "acne vulgaris", "NLRP3 inflammasome", and "Cutibacterium acnes".The reference lists of retrieved articles were also reviewed to identify relevant articles.Key Content and Findings: Cutibacterium acnes infection can lead to a series of inflammatory reactions and the production of inflammatory factors such as interleukin (IL)-1β. In vitro and in vivo studies demonstrated that the NLRP3 inflammasome plays essential roles in acne vulgaris. Further, innate immunity and adaptive immunity pervade the entire pathogenesis of acne vulgaris. Conclusions:The NLRP3 inflammasome may be a potential therapeutic target for acne vulgaris. Future studies are needed to investigate the potential therapeutic effects of NLRP3 inhibitors on acne vulgaris.