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Special Issue "Therapy and Prevention of Atopic Dermatitis and Psoriasis"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 28 February 2020.

Special Issue Editors

Prof. Dr. Masutaka Furue
E-Mail Website
Guest Editor
Department of Dermatology, Kyushu University, Fukuoka, 812-8582, Japan
Interests: atopic dermatitis; psoriasis; immundermatology; melanoma; dioxins
Special Issues and Collections in MDPI journals
Assoc. Prof. Dr. Takeshi Nakahara
E-Mail Website
Co-Guest Editor
Division of Skin Surface Sensing, Department of Dermatology, Kyushu University, Fukuoka, 812-8582, Japan
Interests: atopic dermatitis; urticaria; psoriasis; dendritic cells; itch
Assoc. Prof. Dr. Gaku Tsuji
E-Mail Website
Co-Guest Editor
Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka, 812-8582, Japan
Interests: aryl hydrocarbon receptor; nuclear factor erythroid 2-related factor 2; oxidative stress; psoriasis; atopic dermatitis

Special Issue Information

Dear Colleagues,

The skin is the outermost part of the body, where various external and internal stimuli are interacted. The complex interface reaction is necessary for maintaining the homeostasis of the epidermal and dermal compartments, but its imbalance results in numerous types of inflammatory disorders, such as psoriasis and atopic dermatitis. The excellent therapeutic success of biological treatments stress the pathogenetic importance of TNF-α/IL-23/IL-17 axis for psoriasis, and IL-4/IL-13 signals for atopic dermatitis. Common external stimuli include ultraviolet rays, chemicals, allergens, and environmental pollutants. Some of these agents modulate psoriatic and atopic inflammation by activating the oxidative aryl hydrocarbon receptor, as well as the antioxidative NRF2 transcription factors. Various cytochemokines involved in Th17 and Th2 deviation are also operative in psoriatic and atopic inflammation, respectively, by facilitating the differentiation and recruitent of pathogenic dendritic cells, T-cells, and innate lymphoid cells. In this Special Issue, we will publish cutting-edge information regarding skin inflammation, therapy, and prevention, especially related to psoriatic and atopic inflammation. We warmly welcome your submissions, including original papers and reviews.

Prof. Dr. Masutaka Furue
Assoc. Prof. Dr. Takeshi Nakahara
Assoc. Prof. Dr. Gaku Tsuji
Guest Editor

Manuscript Submission Information

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Keywords

  • Inflammatory skin diseases
  • Psoriasis
  • Atopic dermatitis
  • Environmental pollutants
  • Aryl hydrocarbon receptor
  • NRF2

Published Papers (14 papers)

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Research

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Open AccessArticle
Multifaceted Analyses of Epidermal Serine Protease Activity in Patients with Atopic Dermatitis
Int. J. Mol. Sci. 2020, 21(3), 913; https://doi.org/10.3390/ijms21030913 - 30 Jan 2020
Abstract
The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals [...] Read more.
The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals (n = 46) and AD patients (n = 63) by tape stripping and then measuring the trypsin- and chymotrypsin-like serine protease activity. We also analyzed the p.D386N and p.E420K of SPINK5 variants and loss-of-function mutations of FLG in the AD patients. The serine protease activity in the SC was increased not only in AD lesions but also in non-lesions of AD patients. We found, generally, that there was a positive correlation between the serine protease activity in the SC and the total serum immunoglobulin E (IgE) levels, serum thymus and activation-regulated chemokine (TARC) levels, and peripheral blood eosinophil counts. Moreover, the p.D386N or p.E420K in SPINK5 and FLG mutations were not significantly associated with the SC’s serine protease activity. Epidermal serine protease activity was increased even in non-lesions of AD patients. Such activity was found to correlate with a number of biomarkers of AD. Further investigations of serine proteases might provide new treatments and prophylaxis for AD. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessArticle
The EGFR-ERK/JNK-CCL20 Pathway in Scratched Keratinocytes May Underpin Koebnerization in Psoriasis Patients
Int. J. Mol. Sci. 2020, 21(2), 434; https://doi.org/10.3390/ijms21020434 - 09 Jan 2020
Abstract
Epidermal keratinocytes represent a rich source of C-C motif chemokine 20 (CCL20) and recruit CCR6+ interleukin (IL)-17A–producing T cells that are known to be pathogenic for psoriasis. A previous study revealed that scratch injury on keratinocytes upregulates CCL20 production, which is implicated [...] Read more.
Epidermal keratinocytes represent a rich source of C-C motif chemokine 20 (CCL20) and recruit CCR6+ interleukin (IL)-17A–producing T cells that are known to be pathogenic for psoriasis. A previous study revealed that scratch injury on keratinocytes upregulates CCL20 production, which is implicated in the Koebner phenomenon characteristically seen in psoriasis patients. However, the molecular mechanisms leading to scratch-induced CCL20 production remain elusive. In this study, we demonstrate that scratch injury upregulates the phosphorylation of epidermal growth factor receptor (EGFR) and that the specific EGFR inhibitor PD153035 attenuates scratch-induced CCL20 upregulation in an extracellular signal-related kinase (ERK)-dependent, and to a lesser extent, a c-Jun N-terminal kinase (JNK)-dependent but p38 mitogen-activated protein kinase (MAPK)–independent manner. Immunoreactive CCL20 was visualized in the keratinocytes that lined the scratched wound. IL-17A also induced the phosphorylation of EGFR and further augmented scratch-induced CCL20 upregulation. The EGFR-ERK/JNK-CCL20 pathway in scratched keratinocytes may explain why Koebnerization is frequently seen in psoriasis patients. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessArticle
Differences in Osteoimmunological Biomarkers Predictive of Psoriatic Arthritis among a Large Italian Cohort of Psoriatic Patients
Int. J. Mol. Sci. 2019, 20(22), 5617; https://doi.org/10.3390/ijms20225617 - 10 Nov 2019
Cited by 1
Abstract
(1) Background: In literature it is reported that 20–30% of psoriatic patients evolve to psoriatic arthritis over time. Currently, no specific biochemical markers can either predict progression to psoriatic arthritis or response to therapies. This study aimed to identify osteoimmunological markers applicable to [...] Read more.
(1) Background: In literature it is reported that 20–30% of psoriatic patients evolve to psoriatic arthritis over time. Currently, no specific biochemical markers can either predict progression to psoriatic arthritis or response to therapies. This study aimed to identify osteoimmunological markers applicable to clinical practice, giving a quantitative tool for evaluating pathological status and, eventually, to provide prognostic support in diagnosis. (2) Methods: Soluble (serum) bone and cartilage markers were quantified in 50 patients with only psoriasis, 50 psoriatic patients with psoriatic arthritis, and 20 healthy controls by means of multiplex and enzyme-linked immunoassays. (3) Results: Differences in the concentrations of matrix metalloproteases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), receptor activator of nuclear factor kappa-B- ligand (RANK-L), procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTx-I), dickkopf-related protein 1 (DKK1), and sclerostin (SOST) distinguished healthy controls from psoriasis and psoriatic arthritis patients. We found that MMP2, MMP12, MMP13, TIMP2, and TIMP4 distinguished psoriasis from psoriatic arthritis patients undergoing a systemic treatment, with a good diagnostic accuracy (Area under the ROC Curve (AUC) > 0.7). Then, chitinase-3-like protein 1 (CHI3L1) and MMP10 distinguished psoriasis from psoriatic arthritis not undergoing systemic therapy and, in the presence of onychopathy, MMP8 levels were higher in psoriasis than in psoriatic arthritis. However, in these latter cases, the diagnostic accuracy of the identified biomarkers was low (0.5 < AUC < 0.7). (4) Conclusions. By highlighting never exploited differences, the wide osteoimmunological biomarkers panel provides a novel clue to the development of diagnostic paths in psoriasis and psoriasis-associated arthropathic disease. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessArticle
Butyric Acid from Probiotic Staphylococcus epidermidis in the Skin Microbiome Down-Regulates the Ultraviolet-Induced Pro-Inflammatory IL-6 Cytokine via Short-Chain Fatty Acid Receptor
Int. J. Mol. Sci. 2019, 20(18), 4477; https://doi.org/10.3390/ijms20184477 - 11 Sep 2019
Abstract
The glycerol fermentation of probiotic Staphylococcus epidermidis (S. epidermidis) in the skin microbiome produced butyric acid in vitro at concentrations in the millimolar range. The exposure of dorsal skin of mice to ultraviolet B (UVB) light provoked a significant increased production [...] Read more.
The glycerol fermentation of probiotic Staphylococcus epidermidis (S. epidermidis) in the skin microbiome produced butyric acid in vitro at concentrations in the millimolar range. The exposure of dorsal skin of mice to ultraviolet B (UVB) light provoked a significant increased production of pro-inflammatory interleukin (IL)-6 cytokine. Topical application of butyric acid alone or S. epidermidis with glycerol remarkably ameliorated the UVB-induced IL-6 production. In vivo knockdown of short-chain fatty acid receptor 2 (FFAR2) in mouse skin considerably blocked the probiotic effect of S. epidermidis on suppression of UVB-induced IL-6 production. These results demonstrate that butyric acid in the metabolites of fermenting skin probiotic bacteria mediates FFAR2 to modulate the production of pro-inflammatory cytokines induced by UVB. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessArticle
Altered Lipid Metabolism in Blood Mononuclear Cells of Psoriatic Patients Indicates Differential Changes in Psoriasis Vulgaris and Psoriatic Arthritis
Int. J. Mol. Sci. 2019, 20(17), 4249; https://doi.org/10.3390/ijms20174249 - 30 Aug 2019
Cited by 2
Abstract
The aim of this study was to investigate possible stress-associated disturbances in lipid metabolism in mononuclear cells, mainly lymphocytes of patients with psoriasis vulgaris (Ps, n = 32) or with psoriatic arthritis (PsA, n = 16) in respect to the healthy volunteers (n [...] Read more.
The aim of this study was to investigate possible stress-associated disturbances in lipid metabolism in mononuclear cells, mainly lymphocytes of patients with psoriasis vulgaris (Ps, n = 32) or with psoriatic arthritis (PsA, n = 16) in respect to the healthy volunteers (n = 16). The results showed disturbances in lipid metabolism of psoriatic patients reflected by different phospholipid profiles. The levels of non-enzymatic lipid metabolites associated with oxidative stress 8-isoprostaglandin F2α (8-isoPGF2α) and free 4-hydroxynonenal (4-HNE) were higher in PsA, although levels of 4-HNE-His adducts were higher in Ps. In the case of the enzymatic metabolism of lipids, enhanced levels of endocannabinoids were observed in both forms of psoriasis, while higher expression of their receptors and activities of phospholipases were detected only in Ps. Moreover, cyclooxygenase-1 (COX-1) activity was enhanced only in Ps, but cyclooxygenase-2 (COX-2) was enhanced both in Ps and PsA, generating higher levels of eicosanoids: prostaglandin E1 (PGE1), leukotriene B4 (LTB4), 13-hydroxyoctadecadienoic acid (13HODE), thromboxane B2 (TXB2). Surprisingly, some of major eicosanoids 15-d-PGJ2 (15-deoxy-Δ12,14-prostaglandin J2), 15-hydroxyeicosatetraenoic acid (15-HETE) were elevated in Ps and reduced in PsA. The results of our study revealed changes in lipid metabolism with enhancement of immune system-modulating mediators in psoriatic mononuclear cells. Evaluating further differential stress responses in Ps and PsA affecting lipid metabolism and immunity might be useful to improve the prevention and therapeutic treatments of psoriasis. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessArticle
IL-4 Augments IL-31/IL-31 Receptor Alpha Interaction Leading to Enhanced Ccl 17 and Ccl 22 Production in Dendritic Cells: Implications for Atopic Dermatitis
Int. J. Mol. Sci. 2019, 20(16), 4053; https://doi.org/10.3390/ijms20164053 - 20 Aug 2019
Cited by 2
Abstract
Severe pruritus is a characteristic feature of atopic dermatitis (AD) and is closely related to its activity. Recent studies have shown that IL-31 is a key determinant of pruritus in AD. Anti-IL-31 receptor alpha (IL-31RA) antibody treatment has also been reported to improve [...] Read more.
Severe pruritus is a characteristic feature of atopic dermatitis (AD) and is closely related to its activity. Recent studies have shown that IL-31 is a key determinant of pruritus in AD. Anti-IL-31 receptor alpha (IL-31RA) antibody treatment has also been reported to improve pruritus clinically, subsequently contributing to the attenuation of AD disease activity. Therefore, IL-31 has been thought to be an important cytokine for regulating pruritus and AD disease activity; however, how IL-31 is involved in the immune response in AD has remained largely unknown. Epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) derived from bone marrow cells have been reported to play a critical role in AD pathogenesis. LCs and DCs produce Ccl 17 and Ccl 22, which chemoattract Th2 cells, leading to AD development. Therefore, we aimed to clarify how IL-31/IL-31RA interaction affects Ccl 17 and Ccl 22 production. To test this, we analyzed murine bone marrow-derived DCs (BMDCs) stimulated with IL-4, an important cytokine in AD development. We found that IL-31RA expression was upregulated by IL-4 stimulation in a dose-dependent manner in BMDCs. Furthermore, IL-31 upregulates Ccl 17 and Ccl 22 production in the presence of IL-4, whereas IL-31 stimulation alone did not produce Ccl 17 and Ccl 22. These findings suggest that IL-4 mediates IL-31RA expression and IL-31/IL-31RA interaction augments Ccl 17 and Ccl 22 production in BMDCs, which promotes Th2-deviated immune response in AD. Since we previously reported that soybean tar Glyteer, an aryl hydrocarbon receptor (AHR) ligand, impairs IL-4/Stat 6 signaling in BMDCs, we examined whether Glyteer affects IL-31RA expression induced by IL-4 stimulation. Glyteer inhibited upregulation of IL-31RA expression induced by IL-4 stimulation in a dose-dependent manner. Glyteer also inhibited Ccl 17 and Ccl 22 production induced by IL-4 and IL-31 stimulation. Taken together, these findings suggest that Glyteer treatment may improve AD disease activity by impairing IL-31/IL-31RA interaction in DCs. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessArticle
Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13Rα2 in Keratinocytes
Int. J. Mol. Sci. 2019, 20(13), 3324; https://doi.org/10.3390/ijms20133324 - 06 Jul 2019
Cited by 2
Abstract
The vicious itch–scratch cycle is a cardinal feature of atopic dermatitis (AD), in which IL-13 signaling plays a dominant role. Keratinocytes express two receptors: The heterodimeric IL-4Rα/IL-13Rα1 and IL-13Rα2. The former one transduces a functional IL-13 signal, whereas the latter IL-13Rα2 works as [...] Read more.
The vicious itch–scratch cycle is a cardinal feature of atopic dermatitis (AD), in which IL-13 signaling plays a dominant role. Keratinocytes express two receptors: The heterodimeric IL-4Rα/IL-13Rα1 and IL-13Rα2. The former one transduces a functional IL-13 signal, whereas the latter IL-13Rα2 works as a nonfunctional decoy receptor. To examine whether scratch injury affects the expression of IL-4Rα, IL-13Rα1, and IL-13Rα2, we scratched confluent keratinocyte sheets and examined the expression of three IL-13 receptors using quantitative real-time PCR (qRT-PCR) and immunofluorescence techniques. Scratch injuries significantly upregulated the expression of IL13RA2 in a scratch line number-dependent manner. Scratch-induced IL13RA2 upregulation was synergistically enhanced in the simultaneous presence of IL-13. In contrast, scratch injuries did not alter the expression of IL4R and IL13RA1, even in the presence of IL-13. Scratch-induced IL13RA2 expression was dependent on ERK1/2 and p38 MAPK signals. The expression of IL-13Rα2 protein was indeed augmented in the scratch edge area and was also overexpressed in lichenified lesional AD skin. IL-13 inhibited the expression of involucrin, an important epidermal terminal differentiation molecule. IL-13-mediated downregulation of involucrin was attenuated in IL-13Rα2-overexpressed keratinocytes, confirming the decoy function of IL-13Rα2. Our findings indicate that scratching upregulates the expression of the IL-13 decoy receptor IL-13Rα2 and counteracts IL-13 signaling. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Review

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Open AccessReview
The Role of Th17-Related Cytokines in Atopic Dermatitis
Int. J. Mol. Sci. 2020, 21(4), 1314; https://doi.org/10.3390/ijms21041314 - 15 Feb 2020
Abstract
T helper-17 (Th17) cells, which mainly produce IL-17, are associated with development of various autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and psoriasis. IL-17 and related cytokines are therapeutic targets of these diseases. In atopic dermatitis (AD), Th2 cytokines [...] Read more.
T helper-17 (Th17) cells, which mainly produce IL-17, are associated with development of various autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and psoriasis. IL-17 and related cytokines are therapeutic targets of these diseases. In atopic dermatitis (AD), Th2 cytokines such as IL-4 and IL-13 are regarded to be the main player of the disease; however, Th17 cytokines are also expressed in AD skin lesions. Expression of IL-22 rather than IL-17 is predominant in AD skin, which is contrary to cytokine expression in psoriasis skin. Relatively low IL-17 expression in AD skin can induce relatively low antimicrobial peptide expression, which may be a reason why bacterial infection is frequently seen in AD patients. Failure of clinical trials for investigating the efficacy of anti-IL-12/23 p40 in AD has suggested that IL-17 expressed in skin lesions should not be the main player but a bystander responding to barrier dysfunction. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessReview
Interleukin-17A and Keratinocytes in Psoriasis
Int. J. Mol. Sci. 2020, 21(4), 1275; https://doi.org/10.3390/ijms21041275 - 13 Feb 2020
Abstract
The excellent clinical efficacy of anti-interleukin 17A (IL-17A) biologics on psoriasis indicates a crucial pathogenic role of IL-17A in this autoinflammatory skin disease. IL-17A accelerates the proliferation of epidermal keratinocytes. Keratinocytes produce a myriad of antimicrobial peptides and chemokines, such as CXCL1, CXCL2, [...] Read more.
The excellent clinical efficacy of anti-interleukin 17A (IL-17A) biologics on psoriasis indicates a crucial pathogenic role of IL-17A in this autoinflammatory skin disease. IL-17A accelerates the proliferation of epidermal keratinocytes. Keratinocytes produce a myriad of antimicrobial peptides and chemokines, such as CXCL1, CXCL2, CXCL8, and CCL20. Antimicrobial peptides enhance skin inflammation. IL-17A is capable of upregulating the production of these chemokines and antimicrobial peptides in keratinocytes. CXCL1, CXCL2, and CXCL8 recruit neutrophils and CCL20 chemoattracts IL-17A-producing CCR6+ immune cells, which further contributes to forming an IL-17A-rich milieu. This feed-forward pathogenic process results in characteristic histopathological features, such as epidermal hyperproliferation, intraepidermal neutrophilic microabscess, and dermal CCR6+ cell infiltration. In this review, we focus on IL-17A and keratinocyte interaction regarding psoriasis pathogenesis. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessReview
The Roles of Lipoprotein in Psoriasis
Int. J. Mol. Sci. 2020, 21(3), 859; https://doi.org/10.3390/ijms21030859 - 29 Jan 2020
Abstract
The association between psoriasis and cardiovascular disease risk has been supported by recent epidemiological data. Patients with psoriasis have an increased adjusted relative risk for myocardial infarction. As such, the cardiovascular risk conferred by severe psoriasis may be comparable to what is seen [...] Read more.
The association between psoriasis and cardiovascular disease risk has been supported by recent epidemiological data. Patients with psoriasis have an increased adjusted relative risk for myocardial infarction. As such, the cardiovascular risk conferred by severe psoriasis may be comparable to what is seen with other well-established risk factors, such as diabetes mellitus. Previous studies demonstrated that low-density lipoprotein (LDL) plays critical roles during atherogenesis. It may be caused by the accumulation of macrophages and lipoprotein in the vessel wall. Oxidized LDL (ox-LDL) stimulates the expression of adhesion molecules, such as ICAM-1 and VCAM-1, on endothelial cells and increases the attachment of mononuclear cells and the endothelium. Even though previous evidence demonstrated that psoriasis patients have tortuous and dilated blood vessels in the dermis, which results in the leakage of ox-LDL, the leaked ox-LDL may increase the expression of adhesion molecules and cytokines, and disturb the static balance of osmosis. Therefore, exploration of the relationship between hyperlipidemia and psoriasis may be another novel treatment option for psoriasis and may represent the most promising strategy. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessReview
Immunological Memory of Psoriatic Lesions
Int. J. Mol. Sci. 2020, 21(2), 625; https://doi.org/10.3390/ijms21020625 - 17 Jan 2020
Abstract
The natural course of psoriasis is the appearance of new lesions in the place of previous ones, which disappeared after a successful therapy. Recent studies of psoriasis etiopathogenesis showed that after psoriatic plaques have disappeared, in healthy skin we can still find a [...] Read more.
The natural course of psoriasis is the appearance of new lesions in the place of previous ones, which disappeared after a successful therapy. Recent studies of psoriasis etiopathogenesis showed that after psoriatic plaques have disappeared, in healthy skin we can still find a trace of inflammation in the form of tissue resident memory cells (TRM). They are originally responsible for protection against viral and bacterial infections in non-lymphatic tissues. In psoriatic inflammation, they are characterized by heterogeneity depending on their origin. CD8+ T cells TRM are abundantly present in psoriatic epidermis, while CD4+ TRM preferentially populate the dermis. In psoriasis, epidermal CD8+ TRM cells express CLA, CCR6, CD103 and IL-23R antigen and produce IL-17A during ex vivo stimulation. However, CD4+ CD103+ TRM can also colonize the epidermis and produce IL-22 during stimulation. Besides T cells, Th22 and epidermal DCs proved that epidermal cells in healed skin were still present and functioning after several years of disease remission. It explains the clinical phenomenon of the tendency of psoriatic lesions to relapse in the same location and it allows to develop new therapeutic strategies in the future. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessReview
Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis
Int. J. Mol. Sci. 2019, 20(21), 5424; https://doi.org/10.3390/ijms20215424 - 31 Oct 2019
Cited by 1
Abstract
The aryl hydrocarbon receptor (AHR)/AHR-nuclear translocator (ARNT) system is a sensitive sensor for small molecular, xenobiotic chemicals of exogenous and endogenous origin, including dioxins, phytochemicals, microbial bioproducts, and tryptophan photoproducts. AHR/ARNT are abundantly expressed in the skin. Once activated, the AHR/ARNT axis strengthens [...] Read more.
The aryl hydrocarbon receptor (AHR)/AHR-nuclear translocator (ARNT) system is a sensitive sensor for small molecular, xenobiotic chemicals of exogenous and endogenous origin, including dioxins, phytochemicals, microbial bioproducts, and tryptophan photoproducts. AHR/ARNT are abundantly expressed in the skin. Once activated, the AHR/ARNT axis strengthens skin barrier functions and accelerates epidermal terminal differentiation by upregulating filaggrin expression. In addition, AHR activation induces oxidative stress. However, some AHR ligands simultaneously activate the nuclear factor-erythroid 2-related factor-2 (NRF2) transcription factor, which is a master switch of antioxidative enzymes that neutralizes oxidative stress. The immunoregulatory system governing T-helper 17/22 (Th17/22) and T regulatory cells (Treg) is also regulated by the AHR system. Notably, AHR agonists, such as tapinarof, are currently used as therapeutic agents in psoriasis and atopic dermatitis. In this review, we summarize recent topics on AHR related to atopic dermatitis and psoriasis. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessReview
The Roles of Sex Hormones in the Course of Atopic Dermatitis
Int. J. Mol. Sci. 2019, 20(19), 4660; https://doi.org/10.3390/ijms20194660 - 20 Sep 2019
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by T helper 2 cell (Th2)-shifted abnormal immunity, skin barrier impairment, and pruritus. The prevalence of AD in childhood is slightly higher in boys than in girls; after puberty, the sexual difference is [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by T helper 2 cell (Th2)-shifted abnormal immunity, skin barrier impairment, and pruritus. The prevalence of AD in childhood is slightly higher in boys than in girls; after puberty, the sexual difference is reversed. The female preponderance in all generations exists in intrinsic AD with enhanced Th1 activity and nickel allergy, lacking increased serum IgE or filaggrin mutation. AD is often deteriorated before menstruation. We review the effects of sex hormones on immune responses and skin permeability barrier and propose possible hypotheses for the above phenomena. After puberty, the immune responses of patients are remarkably influenced by sex hormones. Estrogen and progesterone enhance the activities of Th2/regulatory T cell (Treg) but suppress Th1/Th17. Androgens suppress Th1/Th2/Th17 and induce Treg. The skin permeability barrier is fortified by estrogen but is impaired by progesterone and androgens. Dehydroepiandrosterone suppresses Th2 but enhances Th1. The amount of steroid sulfatase converting dehydroepiandrosterone sulfate to dehydroepiandrosterone is higher in women than in men, and thus, women might be more susceptible to the influence of dehydroepiandrosterone. The balance of modulatory effects of sex hormones on immune responses and skin barrier might regulate the course of AD. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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Open AccessReview
Risk Factors for the Development of Psoriasis
Int. J. Mol. Sci. 2019, 20(18), 4347; https://doi.org/10.3390/ijms20184347 - 05 Sep 2019
Cited by 1
Abstract
Psoriasis is an immune-mediated genetic skin disease. The underlying pathomechanisms involve complex interaction between the innate and adaptive immune system. T cells interact with dendritic cells, macrophages, and keratinocytes, which can be mediated by their secreted cytokines. In the past decade, biologics targeting [...] Read more.
Psoriasis is an immune-mediated genetic skin disease. The underlying pathomechanisms involve complex interaction between the innate and adaptive immune system. T cells interact with dendritic cells, macrophages, and keratinocytes, which can be mediated by their secreted cytokines. In the past decade, biologics targeting tumor necrosis factor-α, interleukin (IL)-23, and IL-17 have been developed and approved for the treatment of psoriasis. These biologics have dramatically changed the treatment and management of psoriasis. In contrast, various triggering factors can elicit the disease in genetically predisposed individuals. Recent studies suggest that the exacerbation of psoriasis can lead to systemic inflammation and cardiovascular comorbidity. In addition, psoriasis may be associated with other auto-inflammatory and auto-immune diseases. In this review, we summarize the risk factors, which can be divided into two groups (namely, extrinsic and intrinsic risk factors), responsible for the onset and exacerbation of psoriasis in order to facilitate its prevention. Full article
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis)
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