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Scientific Reports May 2020The integrin αE known as CD103 binds integrin β7 to form the complete heterodimeric integrin molecule αEβ7. CD103 is mainly expressed by lymphocytes within...
The integrin αE known as CD103 binds integrin β7 to form the complete heterodimeric integrin molecule αEβ7. CD103 is mainly expressed by lymphocytes within epithelial tissues of intestine, lung, and skin as well as subsets of mucosal and dermal conventional dendritic cells (cDCs). CD103 has been originally implicated in the attachment of lymphocytes to epithelium in the gut and skin through the interaction with E-cadherin expressed on intestinal epithelial cells, keratinocytes, and Langerhans cells (LCs). However, an impact of CD103 on the cutaneous immune responses and the development of inflammatory skin diseases remains elusive. Here, we report that CD103 regulates the development of psoriasiform dermatitis through the control of the function of cDCs. Deficiency in CD103 exacerbates psoriasiform dermatitis, accompanied by excessive epidermal hyperplasia and infiltration of inflammatory leukocytes. Furthermore, deficiency in CD103 not only accelerates the production of proinflammatory cytokines in psoriatic lesions but also promotes the generation of lymphocytes producing interleukin (IL)-17 in the skin-draining peripheral lymph nodes (PLNs). Under the deficiency in CD103, cDCs localized in PLNs enhance cytokine production following activation. Thus, our findings reveal a pivotal role for CD103 in the control of the function of cDCs to regulate cutaneous inflammation in psoriasiform dermatitis.
Topics: Animals; Antigens, CD; Autoimmunity; Cell Differentiation; Dermatitis; Female; Flow Cytometry; Immunohistochemistry; Integrin alpha Chains; Keratinocytes; Langerhans Cells; Male; Mice, Inbred C57BL; Psoriasis; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 32433498
DOI: 10.1038/s41598-020-65355-9 -
Scientific Reports May 2021Atopic dermatitis (AD) often presents more severely in African Americans (AAs) and with greater involvement of extensor areas. To investigate immune signatures of AD in...
Atopic dermatitis (AD) often presents more severely in African Americans (AAs) and with greater involvement of extensor areas. To investigate immune signatures of AD in AAs with moderate to severe pruritus, lesional and non-lesional punch biopsies were taken from AA patients along with age-, race-, and sex-matched controls. Histology of lesional skin showed psoriasiform dermatitis and spongiotic dermatitis, suggesting both Th2 and Th17 activity. Gene Set Variation Analysis showed upregulation of Th2 and Th17 pathways in both lesional versus non-lesional and lesional versus control (p < 0.01), while Th1 and Th22 upregulation were observed in lesional versus control (p < 0.05). Evidence for a broad immune signature also was supported by upregulated Th1 and Th22 pathways, and clinically may represent greater severity of AD in AA. Furthermore, population-level analysis of data from TriNetX, a global federated health research network, revealed that AA AD patients had higher values for CRP, ferritin, and blood eosinophils compared to age-, sex-, and race-matched controls as well as white AD patients, suggesting broad systemic inflammation. Therefore, AA AD patients may feature broader immune activation than previously thought and may derive benefit from systemic immunomodulating therapies that modulate key drivers of multiple immune pathways.
Topics: Adult; Black or African American; Aged; Case-Control Studies; Cross-Sectional Studies; Dermatitis, Atopic; Female; Humans; Male; Middle Aged; Skin; Th17 Cells; Th2 Cells; Transcriptome
PubMed: 34045476
DOI: 10.1038/s41598-021-90105-w -
Archives of Pathology & Laboratory... Apr 2014Biopsy of the face is rarely done for inflammatory skin diseases, unless the entire process is confined to the face.
CONTEXT
Biopsy of the face is rarely done for inflammatory skin diseases, unless the entire process is confined to the face.
OBJECTIVE
We hypothesized that facial dermatitis has a differential diagnosis that is more limited than the differential diagnosis of inflammatory skin diseases that affect other parts of the body. To our knowledge, the classification of inflammatory skin diseases occurring on the face has never been conducted before in the English literature.
DESIGN
The most-recent 100 facial biopsies of inflammatory skin conditions were retrieved from our files, and the cases were categorized into the main inflammatory skin patterns.
RESULTS
Forty-seven cases (47%) were categorized as interface dermatitis, 2 cases (2%) as psoriasiform dermatitis, 11 cases (11%) as spongiotic dermatitis, 16 cases (16%) as diffuse and nodular dermatitis, 8 cases (8%) as perivascular dermatitis, 14 cases (14%) as folliculitis and perifolliculitis, 1 case (1%) as panniculitis, and 1 case (1%) as fibrosing dermatitis. The number of diagnostic entities represented within each of these patterns was small.
CONCLUSIONS
We believe that facial dermatitis should have its own more-circumscribed differential diagnosis. From a practical viewpoint, many of the inflammatory skin diseases that affect other parts of the body should be excluded from the differential diagnosis after the tissue is determined to be from a facial skin biopsy, and others should not be considered unless the biopsy is from the face.
Topics: Biopsy; Dermatitis, Seborrheic; Diagnosis, Differential; Eczema; Facial Dermatoses; Facial Neoplasms; Folliculitis; Foreign-Body Reaction; Granuloma; Humans; Lymphoma, B-Cell, Marginal Zone; Panniculitis; Pigmentation Disorders; Psoriasis; Rosacea
PubMed: 24678686
DOI: 10.5858/arpa.2013-0055-OA -
Clinical, Cosmetic and Investigational... 2023Epidermal keratinocytes with an abnormal glucose metabolism have been identified in psoriasis. Hexokinase 2 (HK2) is a crucial enzyme involved in glycolytic metabolic...
PURPOSE
Epidermal keratinocytes with an abnormal glucose metabolism have been identified in psoriasis. Hexokinase 2 (HK2) is a crucial enzyme involved in glycolytic metabolic pathways. However, the expression of HK2 and its potential therapeutic effects in psoriasis remains unclear. This study aimed to investigate the expression pattern of HK2 and evaluate its therapeutic effects in psoriasis.
PATIENTS AND METHODS
A gene expression dataset (GSE121212) downloaded from the Gene Expression Omnibus (GEO) database was used to examine the expression of HK2 in psoriasis. HK2 RNA and protein expression were investigated in psoriasis vulgaris (n=5) and healthy (n=5) samples. Immunohistochemistry for HK2 was performed on psoriasis vulgaris (n=22) and healthy skin (n=10) samples. Additionally, HaCaT cells were treated with M5 (interleukin [IL]-17A, tumor necrosis factor-α, IL-1α, IL-22, and Oncostatin-M) to induce a psoriatic inflammation cell model. A mouse model of psoriatic inflammation was established using topical 5% imiquimod cream. Psoriasis-like cells and mouse models were treated with the HK2 inhibitor 3-bromopyruvate (3-BrPA). Cell proliferation, glucose consumption, and lactate production were assessed. Furthermore, the activation of nuclear factor-kappa B (NF-Kb) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was investigated using Western blot analysis.
RESULTS
According to the GEO dataset, HK2 expression was significantly elevated in psoriasis. Upregulation of HK2 in psoriatic tissues was confirmed by quantitative real-time polymerase chain reaction and Western blotting. The immunohistochemistry score for HK2 was higher in psoriatic lesions than in healthy skin. 3-BrPA inhibited the proliferation and glycolysis of M5-stimulated HaCaT cells. Topical 3-BrPA ameliorated imiquimod-induced psoriasis-like dermatitis. Activation of NF-kB and NLRP3 was downregulated by 3-BrPA treatment.
CONCLUSION
Our study revealed that the glycolytic enzyme HK2 was upregulated in psoriasis and that the HK2 inhibitor 3-BrPA exhibited therapeutic effects in psoriasis cell and mouse models.
PubMed: 37965102
DOI: 10.2147/CCID.S435624 -
Indian Journal of Dermatology,... 2018Antihypertensive drugs are prescribed frequently and can cause cutaneous adverse reactions. The exact incidence and frequency of these reactions are unknown. Multiple... (Review)
Review
Antihypertensive drugs are prescribed frequently and can cause cutaneous adverse reactions. The exact incidence and frequency of these reactions are unknown. Multiple antihypertensive drug consumption has contributed to a substantial increase in the number of cutaneous adverse reactions to them. Thus, there is a need for dermatologists and physicians to be aware of the wide range of available antihypertensives and the type of reactions that can be expected. This review article focuses on the various clinical presentations that have been implicated or associated with them. The diagnosis and management have been discussed in brief.
Topics: Antihypertensive Agents; Dermatology; Drug Eruptions; Humans; Skin Diseases
PubMed: 29405133
DOI: 10.4103/ijdvl.IJDVL_992_16 -
Free Radical Biology & Medicine Feb 2018Endogenous electrophilic fatty acids mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction and gene expression. Nitro-fatty...
Endogenous electrophilic fatty acids mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction and gene expression. Nitro-fatty acids and other electrophilic fatty acids may thus be useful for the prevention and treatment of immune-mediated diseases, including inflammatory skin disorders. In this regard, subcutaneous (SC) injections of nitro oleic acid (OA-NO), an exemplary nitro-fatty acid, inhibit skin inflammation in a model of allergic contact dermatitis (ACD). Given the nitration of unsaturated fatty acids during metabolic and inflammatory processes and the growing use of fatty acids in topical formulations, we sought to further study the effect of nitro-fatty acids on cutaneous inflammation. To accomplish this, the effect of topically applied OA-NO on skin inflammation was evaluated using established murine models of contact hypersensitivity (CHS). In contrast to the effects of subcutaneously injected OA-NO, topical OA-NO potentiated hapten-dependent inflammation inducing a sustained neutrophil-dependent inflammatory response characterized by psoriasiform histological features, increased angiogenesis, and an inflammatory infiltrate that included neutrophils, inflammatory monocytes, and γδ T cells. Consistent with these results, HPLC-MS/MS analysis of skin from psoriasis patients displayed a 56% increase in nitro-conjugated linoleic acid (CLA-NO) levels in lesional skin compared to non-lesional skin. These results suggest that nitro-fatty acids in the skin microenvironment are products of cutaneous inflammatory responses and, in high local concentrations, may exacerbate inflammatory skin diseases.
Topics: Administration, Topical; Animals; Dermatitis, Allergic Contact; Disease Models, Animal; Female; Humans; Inflammation; Inflammation Mediators; Mice; Mice, Inbred BALB C; Neutrophils; Oleic Acids; Psoriasis; Skin; Skin Diseases
PubMed: 29132974
DOI: 10.1016/j.freeradbiomed.2017.11.009 -
International Journal of Nanomedicine 2023[This corrects the article DOI: 10.2147/IJN.S165966.].
Erratum: Chitosan-Based Nanoformulated (-)-Epigallocatechin-3-Gallate (EGCG) Modulates Human Keratinocyte-Induced Responses and Alleviates Imiquimod-Induced Murine Psoriasiform Dermatitis [Erratum].
[This corrects the article DOI: 10.2147/IJN.S165966.].
PubMed: 37197027
DOI: 10.2147/IJN.S416060 -
Frontiers in Immunology 2022Transient receptor potential melastatin 4 (TRPM4) is a Ca-activated, monovalent cation channel that is expressed in a wide range of cells. We previously reported two...
Transient receptor potential melastatin 4 (TRPM4) is a Ca-activated, monovalent cation channel that is expressed in a wide range of cells. We previously reported two gain-of-function (GoF) mutations of TRPM4 as the cause of progressive symmetric erythrokeratodermia (PSEK), which shares similar clinical and histopathological features with psoriasis. Using CRISPR/Cas9 technology, we generated TRPM4 mice that have the equivalent mutation to one of the two genetic mutations found in human PSEK (equivalent to human TRPM4). Using this mutant mice, we examined the effects of TRPM4 GoF at the cellular and phenotypic levels to elucidate the pathological mechanisms underlying PSEK. In the absence of experimental stimulation, TRPM4 mice did not show a phenotype. When treated with imiquimod (IMQ), however, TRPM4 mice were predisposed to more severe psoriasiform dermatitis (PsD) than wild-type (WT), which was characterized by greater accumulation of CCR6-expressing γδ T cells and higher mRNA levels of . In TRPM4 mice, dendritic cells showed enhanced migration and keratinocytes exhibited increased proliferation. Moreover, a TRPM4 inhibitor, glibenclamide, ameliorated PsD in WT and TRPM4 mice. Our results indicate elevated TRPM4 activities boosted susceptibility to cutaneous stimuli, likely through elevation of membrane potential and alteration of downstream cellular signaling, resulting in enhanced inflammation. Our results further suggest a possible therapeutic application of TRPM4 inhibitors in psoriasis.
Topics: Mice; Humans; Animals; Gain of Function Mutation; Imiquimod; Psoriasis; Skin; Eczema; TRPM Cation Channels
PubMed: 36341417
DOI: 10.3389/fimmu.2022.1025499 -
Acta Medica Portuguesa May 2020Immune checkpoint inhibitors revolutionized anti-neoplastic treatment. Recently, the European Medicines Agency and the United States Food and Drug Administration... (Review)
Review
INTRODUCTION
Immune checkpoint inhibitors revolutionized anti-neoplastic treatment. Recently, the European Medicines Agency and the United States Food and Drug Administration approved inhibitors of various immune checkpoints, namely the cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 and its ligand. Despite the added benefits in the treatment of several neoplasms, immune checkpoint blockade may also be associated with multiple immune-related adverse events.
MATERIAL AND METHODS
A literature review in PubMed database on the cutaneous toxicity of immune checkpoint inhibitors was performed until April 30, 2019.
RESULTS AND DISCUSSION
A total of 380 articles were initially screened, of which 75 are the basis of this bibliographic review. The immune checkpoint inhibitors monoclonal antibodies produce their beneficial effects by activating the patient's immune system. This activation also results in adverse events that can affect any organ, whereas cutaneous toxicity is the most frequent and precocious. The adverse events of the programmed cell death protein 1 and its ligand and of the cytotoxic T-lymphocyte-associated protein 4 are similar (class effect), despite the apparent higher skin toxicity of inhibitors of the cytotoxic T-lymphocyte-associated protein 4 (or its use in combination with inhibitors of programmed cell death protein 1 and its ligand). The most common cutaneous toxicities are maculopapular exanthema and pruritus, but other more specific adverse effects (e.g. lichenoid or psoriasiform reaction, vitiligo, sarcoidosis, among others) or located in the oral mucosa and/or adnexa are underreported.
CONCLUSION
Given the high rate of cutaneous toxicity associated with new immune checkpoint inhibitors and their impact on quality of life, their early recognition and appropriate approach are crucial in the treatment of cancer patients. Observation by a dermatologist should be provided in patients with certain toxicities.
Topics: Drug Eruptions; Humans; Immune Checkpoint Inhibitors; Neoplasms
PubMed: 32416756
DOI: 10.20344/amp.12424 -
Turk Patoloji Dergisi 2023Pediatric skin diseases may show various manifestations, occasionally affecting the patients' quality of life. Histopathological examination may be required for the...
OBJECTIVE
Pediatric skin diseases may show various manifestations, occasionally affecting the patients' quality of life. Histopathological examination may be required for the diagnosis. The aim of this study was to evaluate the spectrum of clinicopathological features in pediatric skin lesions.
MATERIAL AND METHOD
A total of 368 biopsies of 359 consecutive patients were included. The clinicopathological findings were retrospectively evaluated. Non-neoplastic (inflammatory) lesions (ILs) (n=186) were grouped per their origin, while neoplastic/proliferative lesions (NPLs) (n=182) were grouped based on their pattern. The clinical and histopathological characteristics were statistically analyzed.
RESULTS
51% were male and the median age was 10.4±4.9 years (range 0-17). ILs mainly involved the head and neck, and NPLs were mostly located in the lower extremity (p < 0.001). The most common NPLs were benign nevus (18%, n=33) and pilomatrixoma (15%, n=27), while the most frequent IL was spongiotic/psoriasiform dermatitis (38%). Skin appendage/connective tissue tumors were the largest among NPLs (p=0.02). NPLs were more frequently seen in children > 12 years old compared to ILs (p=0.03). The discordance rate between clinical and histopathological diagnoses was higher for NPLs (27% vs. 15%).
CONCLUSION
Although the spectrum of skin lesions is broad in pediatric patients, most are benign in nature. The higher frequency of melanocytic and/or cystic lesions among children > 12 years old may be attributed to increased self-care during puberty. Neoplastic/proliferative lesions of childhood seem to be less commonly recognized by clinicians, and a multidisciplinary approach remains the optimal method, considering the relatively high rate of discordance between the clinical and histopathological diagnoses.
Topics: Humans; Child; Male; Infant, Newborn; Infant; Child, Preschool; Adolescent; Female; Retrospective Studies; Quality of Life; Skin Neoplasms; Skin; Biopsy
PubMed: 36779578
DOI: 10.5146/tjpath.2023.01599