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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 (31 January 2023) | Viewed by 8508

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Dr. Matthias Peiser

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Guest Editor

Bundesinstitut für Risikobewertung, Berlin, Germany
Interests: in vitro models for skin/food allergy; dendritic cells; co-inhibitory molecules

Special Issue Information

Dear Colleagues,

Inflammatory disorders affecting the human skin including autoimmune and infectious diseases, psoriasis, and allergic contact dermatitis are current challenges for public health and experimental science. Becoming evident in graft rejection of skin explants, individual MHC molecules and a fine-tuned interplay of different subpopulations of immune cells, specific growth factors, cytokines and chemokines is mandatory for skin homeostasis. In case of the disruption of the skin barrier followed by pathogen entry, a complex network of pathogen-recognition receptors and their signals initiates an innate and adaptive immune response resulting in skin inflammation. By increasing knowledge on the mechanistic background, new therapeutic approaches and the development of predictive cell-based immune assays emerge. The focus of this Special Issue is therefore on epidermal and dermal immune populations including keratinocytes; dendritic cells and macrophages; granulocytes; mast cells; innate lymphoid cells; and regulatory and T helper-1, -2 and -17 cells. Human studies and experimental animal and in vitro data in all fields of basic immune and skin allergy research, clinical observations, immunotoxicology are welcome.

Dr. Matthias Peiser
Guest Editor

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Keywords

skin
inflammation
allergy
contact dermatitis
immune system

Published Papers (4 papers)

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Research

12 pages, 6271 KiB

Open AccessArticle

Nickel Challenge In Vitro Affects CD38 and HLA-DR Expression in T Cell Subpopulations from the Blood of Patients with Nickel Allergy

by Metin Artuc, Torsten Zuberbier and Matthias Peiser

Int. J. Mol. Sci. 2024, 25(1), 298; https://doi.org/10.3390/ijms25010298 - 25 Dec 2023

Viewed by 924

Abstract

Nickel allergy is a major health problem and shows clinical manifestation of contact eczema. The response of specific lymphocyte subpopulations in sensitized patients after new challenge to nickel has until now not been studied in detail. To evaluate if nickel-based elicitation reaction could be objectively identified by multi-parametric flow cytometry, immunophenotyping of specific T cells was applied. White blood cells from 7 patients (4 positive in patch test, 3 negative) were challenged by nickel and in vitro short-term culture. Standardized antibody-dye combinations, specific for T helper(h)1, Th17 and cytotoxic T cell activation, were selected according to the recommendations of Stanford Human Immune Monitoring Center. In cytotoxic CD8⁺CCR7⁺CD45RA⁺ T cells from patients suffering from nickel allergy, CD38 and HLA-DR were elevated comparing to healthy donors. After challenge to nickel in vitro both markers decreased in CD8⁺CCR7⁺CD45RA⁺ T cells but found up-regulated in CD4⁺CCR7⁺CD45RA⁺CCR6⁻CXCR3⁺Th1 cells. Intracellular expression of T-bet and RORγt further indicated Th1 and Th17 cells. Finally, CD4⁺CD25⁺CCR4⁻ T cells increased after challenge with nickel in PBMCs of patients with nickel allergy. Flow cytometry based quantification of T cell markers might be used as a specific and reliable method to detect chemical induced skin sensitization and confirm diagnostic patch testing in the clinics. Full article

(This article belongs to the Special Issue Skin Inflammation and Allergy)

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15 pages, 3317 KiB

Open AccessArticle

Lipidome Investigation of Carnosine Effect on Nude Mice Skin to Prevent UV-A Damage

by Beatrice Zoanni, Gilda Aiello, Anne Negre-Salvayre, Giancarlo Aldini, Marina Carini and Alfonsina D’Amato

Int. J. Mol. Sci. 2023, 24(12), 10009; https://doi.org/10.3390/ijms241210009 - 11 Jun 2023

Cited by 3 | Viewed by 1623

Abstract

The lipid profile of skin is fundamental in the maintenance of the protective barrier against the external environment. Signaling and constitutive lipids of this large organ are involved in inflammation, metabolism, aging, and wound healing, such as phospholipids, triglycerides, FFA, and sphingomyelin. Skin exposure to ultraviolet (UV) radiation results in a photoaging process that is an accelerated form of aging. UV-A radiation deeply penetrates the dermis and promotes damage to DNA, lipids, and proteins by increasing the generation of reactive oxygen species (ROS). Carnosine, an endogenous β-alanyl-L-histidine dipeptide, demonstrated antioxidant properties that prevent photoaging and modification of skin protein profiling, making carnosine a compelling ingredient to consider for use in dermatology. The aim of this research was to investigate the modification of skin lipidome after UV-A treatment in presence or not of topic administration of carnosine. Quantitative analyses based on high-resolution mass spectrometry of nude mice skin-extracted lipids resulted in several modifications of barrier composition after UV-A radiation, with or without carnosine treatment. In total, 328 out of 683 molecules showed significant alteration—262 after UV-A radiation and 126 after UV-A and carnosine treatment versus controls. Importantly, the increased oxidized TGs after UV-A radiation, responsible of dermis photoaging, were completely reverted by carnosine application to prevent the UV-A damage. Network analyses also showed that the production of ROS and the calcium and TNF signaling were modulated by UV-A and carnosine. In conclusion, lipidome analyses attested the carnosine activity to prevent the UV-A damage, reducing the lipid oxidation, the inflammation, and the dysregulation of lipid skin barrier. Full article

(This article belongs to the Special Issue Skin Inflammation and Allergy)

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19 pages, 3410 KiB

Open AccessArticle

CREB Is Activated by the SCF/KIT Axis in a Partially ERK-Dependent Manner and Orchestrates Survival and the Induction of Immediate Early Genes in Human Skin Mast Cells

by Kristin Franke, Gürkan Bal, Zhuoran Li, Torsten Zuberbier and Magda Babina

Int. J. Mol. Sci. 2023, 24(4), 4135; https://doi.org/10.3390/ijms24044135 - 18 Feb 2023

Cited by 6 | Viewed by 2265

Abstract

cAMP response element binding protein (CREB) functions as a prototypical stimulus-inducible transcription factor (TF) that initiates multiple cellular changes in response to activation. Despite pronounced expression in mast cells (MCs), CREB function is surprisingly ill-defined in the lineage. Skin MCs (skMCs) are critical effector cells in acute allergic and pseudo-allergic settings, and they contribute to various chronic dermatoses such as urticaria, atopic dermatitis, allergic contact dermatitis, psoriasis, prurigo, rosacea and others. Using MCs of skin origin, we demonstrate herein that CREB is rapidly phosphorylated on serine-133 upon SCF-mediated KIT dimerization. Phosphorylation initiated by the SCF/KIT axis required intrinsic KIT kinase activity and partially depended on ERK1/2, but not on other kinases such as p38, JNK, PI3K or PKA. CREB was constitutively nuclear, where phosphorylation occurred. Interestingly, ERK did not translocate to the nucleus upon SCF activation of skMCs, but a fraction was present in the nucleus at baseline, and phosphorylation was prompted in the cytoplasm and nucleus in situ. CREB was required for SCF-facilitated survival, as demonstrated with the CREB-selective inhibitor 666-15. Knock-down of CREB by RNA interference duplicated CREB’s anti-apoptotic function. On comparison with other modules (PI3K, p38 and MEK/ERK), CREB was equal or more potent at survival promotion. SCF efficiently induces immediate early genes (IEGs) in skMCs (FOS, JUNB and NR4A2). We now demonstrate that CREB is an essential partaker in this induction. Collectively, the ancient TF CREB is a crucial component of skMCs, where it operates as an effector of the SCF/KIT axis, orchestrating IEG induction and lifespan. Full article

(This article belongs to the Special Issue Skin Inflammation and Allergy)

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26 pages, 6408 KiB

Open AccessArticle

Beneficial Effect of Gastrodia elata Blume and Poria cocos Wolf Administration on Acute UVB Irradiation by Alleviating Inflammation through Promoting the Gut-Skin Axis

by Ting Zhang, Shaokai Huang, Jingyi Qiu, Xuangao Wu, Heng Yuan and Sunmin Park

Int. J. Mol. Sci. 2022, 23(18), 10833; https://doi.org/10.3390/ijms231810833 - 16 Sep 2022

Cited by 8 | Viewed by 3070

Abstract

Bioactive compounds in some herbs can, directly and indirectly, protect against photoaging. We evaluated the effects of Gastrodia elata Blume (GE) and Poria cocos Wolf (PC) water extracts on ultraviolet (UV) B-induced skin lesions by acute UVB exposure in ICR mice and explored their mechanism of action. After removing the hair on the back of the mice, UVB (280–310 nm) was exposed to the back for 30 min to induce skin damage. Four UVB exposure groups were divided into the following according to the local application (1,3-butanediol extract) on the dorsal skin and oral intake (0.3 g water extract/kg body weight/day): 1,3-butanediol and cellulose(control; UV-Con), retinoic acid (positive-control; UV-Positive), PC extracts (UV-PC), and GE extracts (UV-GE). The fifth group had no UVB exposure with the same treatment as the UV-Con (Normal-control). The erythema, burns, erosion, and wounds of the UV-PC and UV-PC groups were alleviated, and the most significant improvements occurred in the UV-PC group. PC and GE reduced the thickness of the dorsal skin tissue, the penetration of mast cells, and malondialdehyde contents. The mRNA expression of TNF-α, IL-13, and IL-4, inflammatory factors, were also reduced significantly in the dorsal skin of the UV-PC and UV-GE groups. UV-PC, UV-GE, and UV-Positive showed improvements in UV-induced intestinal tissue inflammation. UV-Con deteriorated the intestinal morphology, and PC and GE alleviated it. The α-diversity of the fecal microbiota decreased in the UV-control, and UV-PC and UV-GE prevented the decrease. Fecal metagenome analysis revealed increased propionate biosynthesis in the UV-PC group but decreased lipopolysaccharide biosynthesis in the UV-PC and UV-GE groups compared to UV-Con. In conclusion, the local application and intake of PC and GE had significant therapeutic effects on acute UV-induced skin damage by reducing oxidative stress and proinflammatory cytokines, potentially promoting the gut-microbiota-gut-skin axis. Full article

(This article belongs to the Special Issue Skin Inflammation and Allergy)

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