Mangiferin, a component of Mangifera indica leaf extracts, inhibits lipid synthesis in human sebocytes.

Inhibition of lipid synthesis in sebocytes is essential for acne treatments. The effects of natural product-derived substances on lipid synthesis are unknown. This study investigated the effects of water extract of Mangifera indica leaves (WEML) on lipid synthesis in human sebocytes. Sebocyte differentiation in low serum conditions increased lipid accumulation and proliferator-activated receptor γ expression. WEML treatment significantly inhibited lipid accumulation and adipogenic mRNA expression in sebocytes. Mangiferin, a bioactive compound in WEML, also reduced lipid accumulation and adipogenic mRNA expression via the AKT pathway. Thus, WEML and mangiferin effectively inhibit lipid synthesis in sebocytes, showing promise for acne treatment.

Inhibition of lipogenesis and sebum secretion for Lotus corniculatus seed extract in vitro and in vivo.

BACKGROUND: Botanical ingredients are widely used in hair- and skin-care products. However, few studies have investigated the effectiveness of botanical products on counteracting sebum synthesis and secretion. OBJECTIVE: To investigate the composition of Lotus corniculatus seed extract (LC) and its potential inhibition of lipogenesis in SZ95 sebocytes and oily human skin. METHODS: The active components of LC solutions were identified by high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). The in vitro effects of LC were evaluated using SZ95 cells treated with linoleic acid (LA) and dihydrotestosterone (DHT) and incubated with LCs for 24 h and 72 h. Lipogenesis was assessed by Oil Red O and Nile Red staining of the cells. In vivo effects were assessed on 30 subjects with oily skin who were enrolled in a randomized, blank-controlled trial and were treated with LC solution for 6 h and 4 weeks. The skin sebum contents and area on the forehead and cheeks were evaluated using a Sebumeter SM815 and Sebfix sebutape with Visioscan VC98. In addition, VISIA was used to collect half-face photos for analysis. RESULTS: A novel active molecule, 5'-o-rhamnosyl uridine, was identified in LC. LC exhibited a dose-dependent inhibitory effect on LA and DHT-induced lipid synthesis. When 5% LC was applied for 3 h, the skin sebum contents and area were significantly reduced compared with the vehicle control, with an obvious reduction after 6 h. Continued use of the serum containing 5% LC for 4 weeks resulted in a significant reduction in the skin sebum contents and area. No adverse reactions were reported during the study. CONCLUSIONS: Topical application of LC resulted in an immediate and long-lasting reduction of the sebum contents and area of oily human skin by reducing sebaceous lipogenesis through the LA and DHT pathways. This indicates the potential of LC as a new biological treatment for oily skin.

CONTEXTE: Les ingrédients végétaux sont largement utilisés dans les produits de soins des cheveux et de la peau. Cependant, peu d'études ont examiné l'efficacité des produits végétaux dans l'inhibition de la synthèse et de la sécrétion de sébum. OBJECTIF: Étudier les composants de l'extrait de graines de lotus (LC) et son effet inhibiteur potentiel sur la lipogenèse des cellules sébacées SZ95 et de la peau grasse. MÉTHODES: Les composants actifs de la solution LC ont été identifiés par chromatographie liquide à haute performance (HPLC) et par résonance magnétique nucléaire (NMR). Les effets de la LC in vitro ont été évalués à l'aide de cellules SZ95 traitées à l'acide linoléique (LA) et à la dihydrotestostérone (DHT) et incubées avec la LC pendant 24 et 72 heures. Les effets in vivo ont été évalués chez 30 sujets à peau grasse qui ont participé à un essai contrôlé randomisé à blanc et qui ont été traités avec une solution de LC pendant 6 heures et 4 semaines. Le sebumeter SM815 et le sebfix sebutape et le visioscan VC98 ont été utilisés pour évaluer la teneur en sébum et la surface de la peau sur le front et les joues. De plus, des photos de demi - visage ont été recueillies pour analyse à l'aide de VISIA. RÉSULTATS: Une nouvelle molécule active, 5'-o-rhamnosyluridine, a été identifiée dans la LC. La LC a un effet inhibiteur dose - dépendant sur la synthèse lipidique induite par LA et DHT. La teneur et la surface du sébum cutané ont été significativement diminuées par rapport à celles du support photographique après 3 heures d'application de 5% de LC, et significativement diminuées après 6 heures. L'utilization de sérum contenant 5% de LC pendant quatre semaines consécutives a entraîné une réduction significative de la teneur en sébum et de la surface de la peau. Aucun effet indésirable n'a été signalé au cours de l'étude. CONCLUSION: L'application topique de LC peut réduire la production de sébum par les voies LA et DHT, ce qui réduit immédiatement et durablement la teneur en sébum et la surface de la peau huileuse humaine. Cela démontre le potentiel de la LC en tant que nouveau traitement biologique de la peau huileuse.

Cutaneous acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia with proliferation of mature sebocytes: A case report.

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma. It has a flat, plaque-like structure and is characterized microscopically by acantholysis and dyskeratosis. Eccrine syringofibroadenomatous hyperplasia is benign and likely reactive. It has recently been considered as a hyperplastic process affecting the eccrine ducts rather than the neoplasm because of its pathological heterogeneity and wide clinical associations. In this article, we present the case of 97-year-old Japanese women with a 10-mm wide, painful acantholytic dyskeratotic acanthoma accompanied by syringofibroadenomatous hyperplasia in the right femoral region. Although syringofibroadenomatous hyperplasia is known to occur as a reactive process with various dermatoses and cutaneous tumors, to date, there have been no reports of cases of acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia. Moreover, this case also includes the unusual finding of an increase in the mature sebocytes in the area of the syringofibroadenomatous hyperplasia.

An updated review of the sebaceous gland and its role in health and diseases Part 1: Embryology, evolution, structure, and function of sebaceous glands.

Sebaceous glands are sebum-secreting components of pilosebaceous units. The embryological development of the sebaceous gland follows that of the hair follicle and epidermal tissue, beginning between weeks 13 and 16 of fetal development. New sebaceous glands do not normally develop following birth, but their size increases with age. Sebocytes express a multitude of hormone receptors and are heavily regulated to secrete sebum by androgens. There is a large increase of sebum excretion at birth and again at puberty, until approximately age 17. In adulthood, sebum production remains stable and declines to zero in postmenopausal women and in men aged 60-70. Besides the production and release of sebum, sebaceous glands function to lubricate the skin and hair, provide thermoregulation, and exhibit antimicrobial activity. Research has shown sebaceous glands to possess the cellular capability to transcribe genes necessary for androgen metabolism. Dysfunction of the sebaceous gland can be seen primarily in steatocystoma simplex and multiplex, sebaceous gland hyperplasia, sebaceoma, sebaceous adenoma, sebaceous carcinoma, nevus sebaceus, and folliculosebaceous cystic hamartoma. Sebaceous glands are secondarily involved in acne vulgaris, seborrheic dermatitis, and androgenic alopecia.

Transcriptional Differences in Lipid-Metabolizing Enzymes in Murine Sebocytes Derived from Sebaceous Glands of the Skin and Preputial Glands.

Sebaceous glands are adnexal structures, which critically contribute to skin homeostasis and the establishment of a functional epidermal barrier. Sebocytes, the main cell population found within the sebaceous glands, are highly specialized lipid-producing cells. Sebaceous gland-resembling tissue structures are also found in male rodents in the form of preputial glands. Similar to sebaceous glands, they are composed of lipid-specialized sebocytes. Due to a lack of adequate organ culture models for skin sebaceous glands and the fact that preputial glands are much larger and easier to handle, previous studies used preputial glands as a model for skin sebaceous glands. Here, we compared both types of sebocytes, using a single-cell RNA sequencing approach, to unravel potential similarities and differences between the two sebocyte populations. In spite of common gene expression patterns due to general lipid-producing properties, we found significant differences in the expression levels of genes encoding enzymes involved in the biogenesis of specialized lipid classes. Specifically, genes critically involved in the mevalonate pathway, including squalene synthase, as well as the sphingolipid salvage pathway, such as ceramide synthase, (acid) sphingomyelinase or acid and alkaline ceramidases, were significantly less expressed by preputial gland sebocytes. Together, our data revealed tissue-specific sebocyte populations, indicating major developmental, functional as well as biosynthetic differences between both glands. The use of preputial glands as a surrogate model to study skin sebaceous glands is therefore limited, and major differences between both glands need to be carefully considered before planning an experiment.

Sebaceous gland: Milestones of 30-year modelling research dedicated to the "brain of the skin".

In 2018, Schneider and Zouboulis analysed the available tools for studying sebaceous gland pathophysiology in vitro. Since then, the interest in this field remains unbroken, as demonstrated by recent reviews on sebaceous gland physiology, endocrinology and neurobiology, the role of sebaceous glands beyond acne, and several original works on different areas of sebaceous gland function, including sebaceous lipogenesis. Landmark developments in the first part of the 30-year modelling research dedicated to the sebaceous gland, which is considered by several scientists as the brain of the skin, were the short-term culture of human sebaceous glands, the culture of human sebaceous gland cells and the development of immortalized sebaceous gland cell lines exhibiting characteristics of normal sebocytes. On the other hand, current developments represent the establishment of sebaceous gland spheroids, the 3D-SeboSkin model of viable skin explants ex vivo, the combination of culture-expanded epidermal stem cells of mice and adult humans to form de novo hair follicles and sebaceous glands, when they are transplanted into excisional wounds in mice, and 3D-printed scaffolds coated with decellularized matrix of adipose-derived mesenchymal stromal cells and SZ95 sebocytes. These novel tools may become useful platforms for better understanding of cellular and molecular mechanisms governing sebocyte biology and sebaceous gland homeostasis, such as the changes in sebum synthesis and composition, the infundibular differentiation and the influence of the innate immunity and the cutaneous microbiome and for identifying potential therapeutic targets of skin diseases affecting the sebaceous glands.

Skin-specific regulation of SREBP processing and lipid biosynthesis by glycerol kinase 5.

The recessive N-ethyl-N-nitrosourea-induced phenotype toku is characterized by delayed hair growth, progressive hair loss, and excessive accumulation of dermal cholesterol, triglycerides, and ceramides. The toku phenotype was attributed to a null allele of Gk5, encoding glycerol kinase 5 (GK5), a skin-specific kinase expressed predominantly in sebaceous glands. GK5 formed a complex with the sterol regulatory element-binding proteins (SREBPs) through their C-terminal regulatory domains, inhibiting SREBP processing and activation. In Gk5toku/toku mice, transcriptionally active SREBPs accumulated in the skin, but not in the liver; they were localized to the nucleus and led to elevated lipid synthesis and subsequent hair growth defects. Similar defective hair growth was observed in kinase-inactive GK5 mutant mice. Hair growth defects of homozygous toku mice were partially rescued by treatment with the HMG-CoA reductase inhibitor simvastatin. GK5 exists as part of a skin-specific regulatory mechanism for cholesterol biosynthesis, independent of cholesterol regulation elsewhere in the body.

Nicotinic acid suppresses sebaceous lipogenesis of human sebocytes via activating hydroxycarboxylic acid receptor 2 (HCA2 ).

Nicotinic acid (NA) activates hydroxycarboxylic acid receptor 2 (HCA2 ), and it is widely used in treating dyslipidaemias. Since its side effects include skin dryness, whereas its deficiency can be accompanied by dyssebacia, characterized by sebaceous gland enlargement, we asked if HCA2 is expressed on human sebocytes, and if NA influences sebocyte functions. By using human immortalized SZ95 sebocytes, we found that non-cytotoxic (≤100 µmol/L; MTT-assay) concentrations of NA had no effect on the homeostatic sebaceous lipogenesis (SLG; Nile Red), but normalized excessive, acne-mimicking SLG induced by several lipogenic agents (arachidonic acid, anandamide, linoleic acid + testosterone; Nile Red; 48-hr treatments). Moreover, it exerted significant anti-proliferative actions (CyQUANT-assay), and increased [Ca2+ ]IC (Fluo-4 AM-based Ca2+ -measurement). Although NA did not prevent the lipopolysaccharide-induced pro-inflammatory response (up-regulation [Q-PCR] and release [ELISA] of several pro-inflammatory cytokines) of the sebocytes, collectively, these data support the concept that NA may be effective in suppressing sebum production in vivo. While exploring the mechanism of the sebostatic actions, we found that sebocytes express HCA2 (Q-PCR, immunofluorescent labelling), siRNA-mediated silencing of which prevented the NA-induced Ca2+ -signal and the lipostatic action. Collectively, our data introduce NA, and HCA2 activators in general, as novel, potent and most likely safe sebostatic agents, with possible anti-acne potential.

Salicylic acid treats acne vulgaris by suppressing AMPK/SREBP1 pathway in sebocytes.

Acne vulgaris is a prevalent cutaneous disease characterized by a multifactorial pathogenic process including hyperseborrhea, inflammation, over-keratinization of follicular keratinocytes and Propionibacterium acnes (P acnes) overgrowth. Salicylic acid (SA), a beta-hydroxy acid, is frequently used in the treatment of acne. SA has been found to decrease skin lipids and to possess anti-inflammatory properties. However, few studies have elucidated the mechanisms and pathways involved in such treatment of acne. In this study, we initially investigated the anti-acne properties of SA in human SEB-1 sebocytes. Treatment with SA decreased sebocyte lipogenesis by downregulating the adenosine monophosphate-activated protein kinase (AMPK)/sterol response element-binding protein-1 (SREBP-1) pathway and reduced inflammation by suppressing the NF-κB pathway in these cells. Salicylic acid also decreased the cell viability of SEB-1 by increasing apoptosis via the death signal receptor pathway. Subsequently, histopathological analysis of a rabbit ear acne model after application of SA for three weeks confirmed that SA suppressed the levels of cytokines and major pathogenic proteins around acne lesions, which supports the mechanisms suggested by our in vitro experiments. These results initially clarified that therapeutic activities of SA in acne vulgaris treatment could be associated with the regulation of SREBP-1 pathway and NF-κB pathway in human SEB-1 sebocytes.

Effect of oral isotretinoin on the nucleo-cytoplasmic distribution of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris.

Oral isotretinoin is the most effective anti-acne drug with the strongest sebum-suppressive effect caused by sebocyte apoptosis. It has been hypothesized that upregulation of nuclear FoxO transcription factors and p53 mediate isotretinoin-induced sebocyte apoptosis in vivo. It is the aim of our study to analyse the distribution of the pro-apoptotic transcription factors FoxO1 and FoxO3 in the nuclear and cytoplasmic compartments of human sebocytes in vivo before and during isotretinoin treatment of acne patients. Immunohistochemical analysis of skin biopsies with antibodies distinguishing phosphorylated and non-phosphorylated human FoxO1 and FoxO3 proteins was performed before isotretinoin treatment, six weeks after initiation of isotretinoin therapy, and in acne-free control patients not treated with isotretinoin. Our in vivo study demonstrates a significant increase in the nucleo-cytoplasmic ratio of non-phosphorylated FoxO1 and FoxO3 during isotretinoin treatment of acne patients. Translational and presented experimental evidence indicates that upregulation of nuclear FoxO1 and FoxO3 proteins is involved in isotretinoin-induced pro-apoptotic signalling in sebocytes confirming the scientific hypothesis of isotretinoin-mediated upregulation of FoxO expression.

Proteolytic activity in the meibomian gland: Implications to health and disease.

The function of the meibomian gland in the upper and lower eyelids is critical to maintaining homeostasis at the ocular surface. Highly specialized meibocytes within the gland must differentiate and accumulate intracellular lipid droplets that are released into the tear film following rupture of the cell membrane. Proteases and their inhibitors have been recognized as key players in remodeling extracellular matrices and promoting the normal integrity of glandular tissue. They modulate a wide range of biological processes, such as cell proliferation and differentiation, and can contribute to disease when aberrantly expressed. Deciphering the role of proteolytic activity in the meibomian gland offers an opportunity to gain a more comprehensive and fundamental understanding of the developmental, physiological, and pathological processes associated with this gland.

Sebocytes differentially express and secrete adipokines.

In addition to producing sebum, sebocytes link lipid metabolism with inflammation at a cellular level and hence, greatly resemble adipocytes. However, so far no analysis was performed to identify and characterize the adipocyte-associated inflammatory proteins, the members of the adipokine family in sebocytes. Therefore, we determined the expression profile of adipokines [adiponectin, interleukin (IL) 6, resistin, leptin, serpin E1, visfatin, apelin, chemerin, retinol-binding protein 4 (RBP4) and monocyte chemoattractant protein 1 (MCP1)] in sebaceous glands of healthy and various disease-affected (acne, rosacea, melanoma and psoriasis) skin samples. Sebaceous glands in all examined samples expressed adiponectin, IL6, resistin, leptin, serpin E1 and visfatin, but not apelin, chemerin, RBP4 and MCP1. Confirming the presence of the detected adipokines in the human SZ95 sebaceous gland cell line we further characterized their expression and secretion patterns under different stimuli mimicking bacterial invasion [by using Toll-like receptor (TLR)2 and 4 activators], or by 13-cis retinoic acid (13CRA; also known as isotretinoin), a key anti-acne agent. With the exception of resistin, the expression of all of the detected adipokines (adiponectin, IL6, leptin, serpin E1 and visfatin) could be further regulated at the level of gene expression, showing a close correlation with the secreted protein levels. Besides providing further evidence on similarities between adipocytes and sebocytes, our results strongly suggest that sebocytes are not simply targets of inflammation but may exhibit initiatory and modulatory roles in the inflammatory processes of the skin through the expression and secretion of adipokines.

Beyond acne: Current aspects of sebaceous gland biology and function.

The sebaceous gland is most commonly found in association with a hair follicle. Its traditional function is the holocrine production of sebum, a complex mixture of lipids, cell debris, and other rather poorly characterized substances. Due to the gland's central role in acne pathogenesis, early research had focused on its lipogenic activity. Less studied aspects of the sebaceous gland, such as stem cell biology, the regulation of cellular differentiation by transcription factors, the significance of specific lipid fractions, the endocrine and specially the neuroendocrine role of the sebaceous gland, and its contribution to the innate immunity, the detoxification of the skin, and skin aging have only recently attracted the attention of researchers from different disciplines. Here, we summarize recent multidisciplinary progress in sebaceous gland research and discuss how sebaceous gland research may stimulate the development of novel therapeutic strategies targeting specific molecular pathways of the pathogenesis of skin diseases.

A novel H­tert immortalized human sebaceous gland cell line (XL-i-20) for the investigation of photodynamic therapy.

BACKGROUND: Acne vulgaris is a species-specific human disease. To date, there has been no established human sebocyte cell line of Asian origin. Our previous study has demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of acne vulgaris, primarily attributed to its cytotoxic properties; however, its regulatory mechanism remains largely unknown. OBJECTIVES: To establish an immortalized human sebocyte cell line derived from Chinese population and investigate the underlying mechanism of ALA-PDT. METHODS: Human primary sebocytes were transfected with the human tert gene (h­tert). The biological characteristics, including cell proliferation, cell markers, and sebum secretion function, were compared between primary sebocytes and the immortalized sebocytes (XL-i-20). Stimulations such as ALA-PDT, were applied respectively to both primary sebocytes and XL-i-20 cells to assess changes in their cellular functions. The transcriptome differences between primary sebocytes and XL-i-20 sebocytes were investigated using RNA-seq analysis. The XL-i-20 cell line was used to establish a sebaceous gland (SG) organoid culture, serving as a representative model of SG for the investigation of ALA-PDT. RESULTS: The h­tert immortalized sebocyte cell line exhibited the ability to be consecutively cultured for more than fifty passages. Both primary and immortalized cells expressed sebocyte markers such as epithelial membrane antigens (EMA, or MUC-1), Cytokeratin 7 (CK7) and adipose differentiation-related protein associated antigens (ADRP), and maintained sebum secretion function. The proliferative capacity of XL-i-20 was found to be significantly higher than that of primary sebocytes. The responses of XL-i-20 to ALA-PDT were indistinguishable from those elicited by primary sebocytes. Cell viability and sebum secretion were decreased after ALA-PDT in both two cell lines, and lipid-related proteins (SREBP-1/PPARγ) were down-regulated. The transcriptome data consistently demonstrated upregulation of genes related to inflammatory responses and downregulation of genes involved in lipid metabolism in both cell types following PDT. The analysis of common differential genes of primary sebocytes and XL-i-20 sebocytes post ALA-PDT showed that TNF signaling pathways, MAPK signaling pathways and JAK-STAT signaling pathways were activated. The SG organoids were spherical, which expressed markers of FANS and PLET1. Ki-67 was down-regulated after ALA-PDT. CONCLUSIONS: We have developed an h­tert immortalized sebocyte cell line from an Asian population. The cell line, XL-i-20, maintains the essential characteristics of its parent primary sebocytes. Moreover, XL-i-20 sebocyte exhibited a significant respond to ALA-PDT, demonstrating comparable phenotypic and molecular changes to primary sebocytes. Therefore, XL-i-20 and its derived SG organoid serve as appropriate in vitro models for investigating the efficacy and mechanisms of ALA-PDT in SG-related diseases.

In vitro acne disease model from inertial focusing effect for studying the interactions between sebocyte glands and macrophages.

Acne is one of the most widespread skin diseases. The acne mechanism is intricate, involving interactions between different types of cells (i.e., sebocytes and macrophages). One of the challenges in studying the mechanism of acne is that current in vitro culture methods cannot reflect the 3D cellular environment in the tissue, including inflammatory stimuli and cellular interactions especially the interactions between sebocytes and immune cells. To solve this issue, we generated an in vitro acne disease model consisting of 3D artificial sebocyte glands and macrophages through the inertial focusing effect method. Using this model, we produced a controllable inflammatory environment similar to the acne pathogenetic process in the skin. The 3D artificial sebocyte glands and macrophages can be separated for analyzing each cell type, assisting the in-depth understanding of the acne mechanism. This study indicates that proinflammatory macrophages promote lipid accumulation and induce oxidative stress in sebocyte glands. Additionally, in an inflammatory environment, sebocyte glands induce macrophage polarization into the M1 phenotype. Employing this model for drug screening, we also demonstrated that, cannabidiol (CBD), a clinically investigated drug, is effective in restoring lipid accumulation, oxidative stress, inflammatory cytokines and macrophage polarization in the acne disease.

3D artificial sebocyte glands from inertial focusing effect for facile and flexible analysis of light damage and drug screening.

The sebaceous gland is a neuro-immuno-endocrine organ responsible for maintaining regular skin functions. Overdose exposure of UV and visible light (e.g., blue light) can cause sebocyte gland function disorders or even different diseases (e.g., chronic actinic dermatitis). Studying the mechanism of light-induced damage in sebaceous glands has been challenging, since ex vivo culture of sebaceous glands is difficult due to its short life in culture medium. To address this issue, a versatile 3D artificial sebocyte gland model was established using the inertial focusing effect for studying the impact of light damage and screening potential drugs. The artificial sebocyte gland exhibited specific biological function and structure similar to natural sebocyte glands. Using this artificial sebocyte gland, the interactions between the artificial organ and blue light or UV were studied. The results indicated that UV and blue light upregulated lipid secretion and downregulated cell viability within the sebocytes. Light damage intensified oxidative stress and promoted pro-inflammation cytokines (i.e., IL-1ß and TNF-α) production in the artificial sebocytes. Additionally, the therapeutic effects of cannabidiol, a clinically tested drug for treating acne, was also indicated on restoring light damaged sebaceous gland functions. These results indicate that the 3D artificial sebocyte gland could be a versatile, fast, and low-cost platform for skincare studies or drug screening.

Distinct mechanisms for sebaceous gland self-renewal and regeneration provide durability in response to injury.

Sebaceous glands (SGs) release oils that protect our skin, but how these glands respond to injury has not been previously examined. Here, we report that SGs are largely self-renewed by dedicated stem cell pools during homeostasis. Using targeted single-cell RNA sequencing, we uncovered both direct and indirect paths by which resident SG progenitors ordinarily differentiate into sebocytes, including transit through a Krt5+PPARγ+ transitional basal cell state. Upon skin injury, however, SG progenitors depart their niche, reepithelialize the wound, and are replaced by hair-follicle-derived stem cells. Furthermore, following targeted genetic ablation of >99% of SGs from dorsal skin, these glands unexpectedly regenerate within weeks. This regenerative process is mediated by alternative stem cells originating from the hair follicle bulge, is dependent upon FGFR2 signaling, and can be accelerated by inducing hair growth. Altogether, our studies demonstrate that stem cell plasticity promotes SG durability following injury.

Sebaceous immunobiology - skin homeostasis, pathophysiology, coordination of innate immunity and inflammatory response and disease associations.

This review presents several aspects of the innovative concept of sebaceous immunobiology, which summarizes the numerous activities of the sebaceous gland including its classical physiological and pathophysiological tasks, namely sebum production and the development of seborrhea and acne. Sebaceous lipids, which represent 90% of the skin surface lipids in adolescents and adults, are markedly involved in the skin barrier function and perifollicular and dermal innate immune processes, leading to inflammatory skin diseases. Innovative experimental techniques using stem cell and sebocyte models have clarified the roles of distinct stem cells in sebaceous gland physiology and sebocyte function control mechanisms. The sebaceous gland represents an integral part of the pilosebaceous unit and its status is connected to hair follicle morphogenesis. Interestingly, professional inflammatory cells contribute to sebocyte differentiation and homeostasis, whereas the regulation of sebaceous gland function by immune cells is antigen-independent. Inflammation is involved in the very earliest differentiation changes of the pilosebaceous unit in acne. Sebocytes behave as potent immune regulators, integrating into the innate immune responses of the skin. Expressing inflammatory mediators, sebocytes also contribute to the polarization of cutaneous T cells towards the Th17 phenotype. In addition, the immune response of the perifollicular infiltrate depends on factors produced by the sebaceous glands, mostly sebaceous lipids. Human sebocytes in vitro express functional pattern recognition receptors, which are likely to interact with bacteria in acne pathogenesis. Sex steroids, peroxisome proliferator-activated receptor ligands, neuropeptides, endocannabinoids and a selective apoptotic process contribute to a complex regulation of sebocyte-induced immunological reaction in numerous acquired and congenital skin diseases, including hair diseases and atopic dermatitis.