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Skin Allergy and Immunology
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Skin Allergy and Immunology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 32084

Special Issue Editors

Dr. Hideo Hashizume

E-Mail Website
Guest Editor
Department of Dermatology, Shimada Municipal Hospital, Shizuoka, Japan
Interests: dermatology; allergy; anaphylaxis; immunology; drug hypersensitivity
Special Issues, Collections and Topics in MDPI journals
Dr. Taisuke Ito

E-Mail Website
Guest Editor
Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Interests: skin; T lymphocytes; dermatology; immunity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Skin resides the boundaries between outer and inside of the body, repelling invadors immunologically and retaining water for keeping important functional biochemicals. Breaking down the mechanistic functions may cause various skin diseases. Easy access to skin allows to take efficient skin sample specimens and conduct extensive research on skin microenvironment under physiolosical and pathogenic conditions. Recent mainstay of therapeutic strategy is targeting critical biological molecules in chronic skin inflammatory disorders such as atopic dermatitis and psoriasis. This not only brings remarkable effects on them but also reveals novel functions and cryptic roles of such molecules. Conprehensive genome analysis disclosed a novel pathogenic gene and its critical role of the pathogenesis of autoinflammatory skin disorders. New computer technology of analysing conformational relationships between HLA and drugs has revealed novel mechanisms of the pathogenesis of drug hypersensitivity. We have learned much from exellent studies on skin diseases and clinical experience of novel treatments, inspiring many researchers as a pioneer in medical scinence.

This issue of the International Journal of Molecular Sciences will focus on “skin allergy and immunology”, including new insight into the pathogenesis and treatment of immune-mediated skin disorders. New data on allergy and immune-mediated skin diseases are welcome.

Dr. Hideo Hashizume
Dr. Taisuke Ito
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Allergy
  • Drug hypersensitivity
  • Atopic dermatitis
  • Psoriasis

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Published Papers (7 papers)

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Editorial

Jump to: Research, Review

3 pages, 183 KiB  
Editorial
Current Understanding of Immunological Skin Diseases: Atopic Dermatitis, Generalized Anhidrosis, and Drug Hypersensitivity
by Hideo Hashizume
Int. J. Mol. Sci. 2022, 23(14), 7563; https://doi.org/10.3390/ijms23147563 - 8 Jul 2022
Viewed by 1169
Abstract
Recent dermatological research has progressed, particularly novel technologies and analytical methodologies, providing great advances in the exploration of previously poorly understood interactions between the skin—the outermost surface of humans—and the external environment [...] Full article
(This article belongs to the Special Issue Skin Allergy and Immunology)

Research

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13 pages, 3031 KiB  
Article
Cera Flava Alleviates Atopic Dermatitis by Activating Skin Barrier Function via Immune Regulation
by Gunhyuk Park, Byeong Cheol Moon, Goya Choi and Hye-Sun Lim
Int. J. Mol. Sci. 2021, 22(14), 7531; https://doi.org/10.3390/ijms22147531 - 14 Jul 2021
Cited by 10 | Viewed by 3207
Abstract
Cera Flava (CF), a natural extract obtained from beehives, is widely used in dermatological products owing to its wound healing, wrinkle reduction, UV-protective, and skin cell turnover stimulation effects. However, its effect on AD-like skin lesions is unknown. In this study, we used [...] Read more.
Cera Flava (CF), a natural extract obtained from beehives, is widely used in dermatological products owing to its wound healing, wrinkle reduction, UV-protective, and skin cell turnover stimulation effects. However, its effect on AD-like skin lesions is unknown. In this study, we used a mouse model of AD to evaluate the effects of CP at the molecular and phenotypic levels. Topical house dust mite (HDM) sensitization and challenge were performed on the dorsal skin of NC/Nga mice to induce AD-like cutaneous lesions, phenotypes, and immunologic responses. The topical application of CF for 6 weeks relieved HDM-induced AD-like phenotypes, as quantified by the dermatitis severity score, scratching frequency, and skin moisture. CP decreased immunoglobulin E, histamine, and thymic stromal lymphopoietin levels. Histopathological analysis showed that CF decreased epidermal thickening and the number of mast cells. CF attenuated HDM-induced changes in the expression of skin barrier-related proteins. Furthermore, CF decreased the mRNA levels of inflammatory factors, including interleukin (IL)-1β, IL-4, IL-13, IL-8, TARC, MDC, and RANTES, in dorsal skin tissue via the TLR2/MyD88/TRAF6/ERK pathway. CF influences skin barrier function and immune regulation to alleviate AD symptoms. It may therefore be an effective alternative to topical steroids for the treatment of AD. Full article
(This article belongs to the Special Issue Skin Allergy and Immunology)
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15 pages, 11209 KiB  
Article
Role of Multiple Comorbidities and Therapies in Conditioning the Clinical Severity of DRESS: A Mono-Center Retrospective Study of 25 Cases
by Andrea Toniato, Chiara Gamba, Jan Walter Schroeder, Valeria Fabbri, Scarlett Valeria Bernal Ortiz, Linda Borgonovo, Marta Piantanida, Joseph Scibilia, Luca Balossi, Eleonora Brusamolino, Emanuela Bonoldi, Valentina Caputo, Michele Nichelatti and Elide Anna Pastorello
Int. J. Mol. Sci. 2021, 22(13), 7072; https://doi.org/10.3390/ijms22137072 - 30 Jun 2021
Cited by 6 | Viewed by 2657
Abstract
DRESS/DiHS is a complex and potentially fatal drug reaction. Little is known about risk factors and elements that can help to identify patients with a severe reaction early. The aim of the study was to investigate those factors favoring the disease and its [...] Read more.
DRESS/DiHS is a complex and potentially fatal drug reaction. Little is known about risk factors and elements that can help to identify patients with a severe reaction early. The aim of the study was to investigate those factors favoring the disease and its severity by analyzing the clinical conditions and therapies preceding the reaction. We conducted a retrospective analysis on patients admitted to our center between 2010 and 2020 who were discharged with a diagnosis of DRESS. We used the RegiSCAR diagnostic criteria. We defined the severity of DRESS using the criteria of Mizukawa et al. We included 25 patients (15 females) with a median age of 66 years. Skin involvement, eosinophilia, and liver injury were the most important aspects. Allopurinol was found to be the most involved drug. Reaction severity was significantly associated with the number of daily medications (p = 0.0067) and an age of at least 68 years (p = 0.013). In addition, 75% of severe cases had at least three comorbidities in history, and most of the severe cases were female. In our study the advanced age, the high number of comorbidities and home therapies, and the inflammatory state were found to be predisposing elements to the development of the disease and its severity. Full article
(This article belongs to the Special Issue Skin Allergy and Immunology)
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11 pages, 1770 KiB  
Article
Ubiquitous Overexpression of Chromatin Remodeling Factor SRG3 Exacerbates Atopic Dermatitis in NC/Nga Mice by Enhancing Th2 Immune Responses
by Sung Won Lee, Hyun Jung Park, Jungmin Jeon, Yun Hoo Park, Tae-Cheol Kim, Sung Ho Jeon, Rho Hyun Seong, Luc Van Kaer and Seokmann Hong
Int. J. Mol. Sci. 2021, 22(4), 1553; https://doi.org/10.3390/ijms22041553 - 4 Feb 2021
Cited by 9 | Viewed by 2847
Abstract
The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 [...] Read more.
The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3β-actin mice). We found that SRG3β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis. Full article
(This article belongs to the Special Issue Skin Allergy and Immunology)
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Review

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30 pages, 3248 KiB  
Review
The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis
by Pamela Gallegos-Alcalá, Mariela Jiménez, Daniel Cervantes-García and Eva Salinas
Int. J. Mol. Sci. 2021, 22(19), 10661; https://doi.org/10.3390/ijms221910661 - 1 Oct 2021
Cited by 23 | Viewed by 9248
Abstract
The keratinocyte (KC) is the main functional and structural component of the epidermis, the most external layer of the skin that is highly specialized in defense against external agents, prevention of leakage of body fluids and retention of internal water within the cells. [...] Read more.
The keratinocyte (KC) is the main functional and structural component of the epidermis, the most external layer of the skin that is highly specialized in defense against external agents, prevention of leakage of body fluids and retention of internal water within the cells. Altered epidermal barrier and aberrant KC differentiation are involved in the pathophysiology of several skin diseases, such as atopic dermatitis (AD). AD is a chronic inflammatory disease characterized by cutaneous and systemic immune dysregulation and skin microbiota dysbiosis. Nevertheless, the pathological mechanisms of this complex disease remain largely unknown. In this review, we summarize current knowledge about the participation of the KC in different aspects of the AD. We provide an overview of the genetic predisposing and environmental factors, inflammatory molecules and signaling pathways of the KC that participate in the physiopathology of the AD. We also analyze the link among the KC, the microbiota and the inflammatory response underlying acute and chronic skin AD lesions. Full article
(This article belongs to the Special Issue Skin Allergy and Immunology)
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12 pages, 3289 KiB  
Review
Acquired Idiopathic Generalized Anhidrosis (AIGA) and Its Complications: Implications for AIGA as an Autoimmune Disease
by Reiko Kageyama, Tetsuya Honda and Yoshiki Tokura
Int. J. Mol. Sci. 2021, 22(16), 8389; https://doi.org/10.3390/ijms22168389 - 4 Aug 2021
Cited by 19 | Viewed by 5589
Abstract
Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder in which systemic anhidrosis/hypohidrosis occurs without causative dermatological, metabolic or neurological disorder. Most cases of AIGA have been reported in Asia, especially in Japan, but there have been only a few reports in Europe [...] Read more.
Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder in which systemic anhidrosis/hypohidrosis occurs without causative dermatological, metabolic or neurological disorder. Most cases of AIGA have been reported in Asia, especially in Japan, but there have been only a few reports in Europe and the United States. Severe AIGA may result in heatstroke and can reduce quality of life due to restriction of exercise and outdoor works. AIGA is often accompanied by cholinergic urticaria (CholU), and it is thought that AIGA and CholU with anhidrosis/hypohidrosis belong to the same spectrum of the disease. However, the pathophysiology of AIGA has not yet been clarified. Decreased expression of cholinergic receptor M3 on the epithelial cells of eccrine sweat glands is often accompanied by T cell infiltration around eccrine apparatus, suggesting an immunological mechanism of disordered perspiration. AIGA is occasionally associated with various complications indicative of autoimmune disorders. The association of autoimmune complications further suggests that AIGA is an autoimmune disorder. Studies on complications may lead to a better understanding of the pathophysiology of AIGA. Full article
(This article belongs to the Special Issue Skin Allergy and Immunology)
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13 pages, 1406 KiB  
Review
Current Perspective Regarding the Immunopathogenesis of Drug-Induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms (DIHS/DRESS)
by Fumi Miyagawa and Hideo Asada
Int. J. Mol. Sci. 2021, 22(4), 2147; https://doi.org/10.3390/ijms22042147 - 21 Feb 2021
Cited by 66 | Viewed by 6052
Abstract
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe type of adverse drug eruption associated with multiorgan involvement and the reactivation of human herpesvirus 6, which arises after prolonged exposure to certain drugs. Typically, two waves of disease activity [...] Read more.
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe type of adverse drug eruption associated with multiorgan involvement and the reactivation of human herpesvirus 6, which arises after prolonged exposure to certain drugs. Typically, two waves of disease activity occur during the course of DIHS/DRESS; however, some patients experience multiple waves of exacerbation and remission of the disease. Severe complications, some of which are related to cytomegalovirus reactivation, can be fatal. DIHS/DRESS is distinct from other drug reactions, as it involves herpes virus reactivation and can lead to the subsequent development of autoimmune diseases. The association between herpesviruses and DIHS/DRESS is now well established, and DIHS/DRESS is considered to arise as a result of complex interactions between several herpesviruses and comprehensive immune responses, including drug-specific immune responses and antiviral immune responses, each of which may be mediated by distinct types of immune cells. It appears that both CD4 and CD8 T cells are involved in the pathogenesis of DIHS/DRESS but play distinct roles. CD4 T cells mainly initiate drug allergies in response to drug antigens, and then herpesvirus-specific CD8 T cells that target virus-infected cells emerge, resulting in tissue damage. Regulatory T-cell dynamics are also suggested to contribute to the diverse symptoms of DIHS/DRESS. However, the pathomechanisms of this complex disease remain largely unknown. In particular, how viral infections contribute to the pathogenesis of DIHS/DRESS and why autoimmune sequelae arise in DIHS/DRESS are yet to be elucidated. This review describes the clinical features of DIHS/DRESS, including the associated complications and sequelae, and discusses recent advances in our understanding of the immunopathogenic mechanisms of DIHS/DRESS. Full article
(This article belongs to the Special Issue Skin Allergy and Immunology)
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