Background Allergen-specific immunotherapy (allergen-SIT) is the only treatment directed at the cause of IgE-mediated allergic diseases. However, there is controversy over the use of SIT for patients ...with atopic dermatitis. Objective We performed a systematic review and meta-analysis to assess the efficacy of SIT for patients with atopic dermatitis. Methods We performed manual searches of reference lists and computerized searches of the MEDLINE, EMBASE, CINAHL, Web of Science, and Cochrane databases (through December 10, 2012) for randomized controlled trials that compared SIT with placebo for patients with atopic dermatitis. The outcome of interest was a dichotomous variable, in terms of treatment success; a meta-analysis was performed by using a random-effects analysis. Subgroup analyses were carried out to evaluate the effects of long-term treatment (more than 1 year), SIT for severe atopic dermatitis, SIT for children, and subcutaneous and sublingual administration of immunotherapy. Results We analyzed 8 randomized controlled trials that comprised a total of 385 subjects. We found that SIT has a significant positive effect on atopic dermatitis (odds ratio OR, 5.35; 95% CI, 1.61-17.77; number needed to treat, 3; 95% CI, 2-9). SIT also showed significant efficacy in long-term treatment (OR, 6.42; 95% CI, 1.50-27.52) for patients with severe atopic dermatitis (OR, 3.13; 95% CI, 1.31-7.48), and when administered subcutaneously (OR, 4.27; 95% CI, 1.36-13.39). Conclusions A meta-analysis provides moderate-level evidence for the efficacy of SIT against atopic dermatitis. However, these findings are based on an analysis of a small number of randomized controlled trials, with considerable heterogeneity among trials.
Although memory T cells within barrier tissues can persist as permanent residents, at least some exchange with blood. The extent to which this occurs is unclear. Here we show that memory CD4(+) T ...cells in mouse skin are in equilibrium with the circulation at steady state. These cells are dispersed throughout the inter-follicular regions of the dermis and form clusters with antigen presenting cells around hair follicles. After infection or administration of a contact sensitizing agent, there is a sustained increase in skin CD4(+) T-cell content, which is confined to the clusters, with a concomitant CCL5-dependent increase in CD4(+) T-cell recruitment. Skin CCL5 is derived from CD11b(+) cells and CD8(+) T cells, with the elimination of the latter decreasing CD4(+) T-cell numbers. These results reveal a complex pattern of tissue-retention and equilibration for CD4(+) memory T cells in skin, which is altered by infection and inflammation history.
Ambient air particulate matter (PM) induces senescence in human skin cells. However, the underlying mechanisms remain largely unknown. We investigated how epigenetic regulatory mechanisms participate ...in cellular senescence induced by PM with a diameter <2.5 (PM
) in human keratinocytes and mouse skin tissues. PM
-treated cells exhibited characteristics of cellular senescence. PM
induced a decrease in DNA methyltransferase (DNMT) expression and an increase in DNA demethylase (ten-eleven translocation; TET) expression, leading to hypomethylation of the p16
promoter region. In addition, PM
led to a decrease in polycomb EZH2 histone methyltransferase expression, whereas the expression of the epigenetic transcriptional activator MLL1 increased. Furthermore, binding of DNMT1, DNMT3B, and EZH2 to the promoter region of p16
decreased in PM
-treated keratinocytes, whereas TET1 and MLL1 binding increased, leading to decreased histone H3 lysine 27 trimethylation (H3K27Me3) and increased H3K4Me3 in the promoter of p16
. PM
-induced senescence involved aryl hydrocarbon receptor (AhR)-induced reactive oxygen species (ROS) production. ROS scavenging dampened PM
-induced cellular senescence through regulation of DNA and histone methylation. Altogether, our work shows that skin senescence induced by environmental PM
occurs through ROS-dependent the epigenetic modification of senescence-associated gene expression. Our findings provide information for the design of preventive and therapeutic strategies against skin senescence, particularly in light of the increasing problem of PM
exposure due to air pollution.
House dust mite (HDM) is the most common allergen exacerbating atopic dermatitis (AD), and allergen-specific immunotherapy (AIT) using HDM exhibited significant improvements in previous studies. ...Alopecia can occur as a complication of AD. Alopecia totalis (AT), a severe form of alopecia areata (AA), does not respond well to treatment and the chance of full recovery is less than 10%. For extensive hair loss, topical immunotherapy such as diphenylcyclopropenone (DPCP) is used as the first-line treatment. However, since DPCP is a kind of contact allergen, it has the potential to exacerbate AD. A 38-year-old man with AD and AA visited our clinic with symptoms worsening from 3 months ago. Although taking oral methylprednisolone (8 mg/day) and cyclosporine (100 mg/day) for 3 months, he has lost over 90% of his hair and the Eczema Area and Severity Index (EASI) was 43. Total serum immunoglobulin E (IgE) levels were 4454 kU/L (normal <100 kU/L) and the specific IgE levels for Dermatophagoides pteronyssinus and Dermatophagoides farinae following ImmunoCAP® were 20.8 and 37.4 kU/L, respectively. This patient did not respond well to previous treatment and was reluctant to use long-term steroids, so subcutaneous AIT using HDM was administered along with oral cyclosporine (100 mg/day). Topical tacrolimus was also applied to the AD lesions throughout the body. To reduce itching, nonsedative antihistamines were used if necessary. Hair loss was almost completely improved 1 year after the AIT initiation and the skin lesions of AD also improved (EASI 2.4). The specific IgE levels for D. pteronyssinus and D. farinae were 3.73 and 7.16 kU/L, respectively. Herein, we report a patient with promising results following AIT for AT with severe AD. In severe alopecic patients with AD refractory to conventional treatment, including immunosuppressants, AIT could be considered as a treatment option.
Particulate matter (PM) increases levels of pro-inflammatory cytokines, but its effects on the skin remain largely unknown. We investigated the signal transduction pathway and epigenetic regulatory ...mechanisms underlying cellular inflammation induced by PM with a diameter of ≤ 2.5 (PM
) in vitro and in vivo. PM
-treated skin keratinocytes produced various inflammatory cytokines, including IL-6. The binding of PM
to TLR5 initiated intracellular signaling through MyD88, and led to the translocation of NFκB to the nucleus, where it bound the NFκB site within IL-6 promoter. Furthermore, PM
induced a direct interaction between TLR5 and NOX4, and in turn induced the production of ROS and activated NFκB-IL-6 downstream, which was prevented by siRNA-mediated knockdown of NOX4 or antioxidant treatment. Furthermore, expression of TLR5, MyD88, NOX4, phospho-NFκB, and IL-6 was increased in skin tissue of PM
-treated flaky tail mice. PM
-induced increased transcription of IL-6 was regulated via DNA methylation and histone methylation by epigenetic modification; the binding of DNA demethylase and histone methyltransferase to the IL-6 promoter regions resulted in increased IL-6 mRNA expression. Our findings provide deep insight into the pathogenesis of PM
exposure and can be used as a therapeutic strategy to treat inflammatory skin diseases caused by PM
exposure.
Background
Atopic dermatitis (AD) is a chronic inflammatory skin disease whose pathogenesis, cause, and treatment have been extensively studied. The association of AD with Th2 cytokines is well ...known; therefore, the analysis of this association is crucial for the diagnosis and treatment of AD. This study aimed to present a new method for measuring protein biomarkers in patients with AD, before and after treatment, using minimally invasive microneedles.
Materials and methods
First, hyaluronic acid‐loaded microneedle patches (HA‐MNs) for skin sample collection were fabricated. Next, after Institutional Review Board approval, 20 patients with AD were recruited and skin samples were taken before and after treatment using four different sampling techniques: (1) tape stripping, (2) hydrocolloid patches, (3) hollow microneedles, and (4) HA‐MNs. Lastly, proteins were isolated from the collected samples, and AD‐related biomarkers were analyzed by enzyme‐linked immunosorbent assay.
Results
Proteins were successfully extracted from the skin samples collected by tape stripping, hydrocolloid patches, and HA‐MNs, except hollow microneedles. Interleukin (IL)‐4, IL‐13, and interferon‐γ were detected in the HA‐MNs only. By comparing the biomarker level correlation before and after treatment and the improvement score of the patients, we observed a significant negative correlation between IL‐4 and IL‐13 with an improvement in AD symptoms.
Conclusion
Overall, our results verified that HA‐MNs can be used to effectively analyze protein levels of biomarkers from skin metabolites of patients with AD and can be applied to monitor the treatment progress of patients with AD in a minimally invasive manner.
Background
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by defective skin barrier and Th2 immune responses. Chitinase 3‐like 1 (CHI3L1), also known as breast ...regression protein 39 (BRP‐39) in mice and human homologue YKL‐40, plays important roles in Th2 inflammation and allergen sensitization. CHI3L1 has been implicated in a variety of diseases including asthma characterized by inflammation, apoptosis and tissue remodelling, but its role in AD remains elusive.
Objective
The aim of this study was to investigate the role of CHI3L1 in the development and progression of AD.
Results
We investigated YKL‐40 levels in the serum and skin of AD patients by ELISA and immunofluorescence, respectively. Using a murine model of AD induced by ovalbumin (OVA), we investigated Th2 immune responses, M2 macrophage activation and skin barrier gene expression using wild‐type (WT) and BRP‐39 null mutant (BRP‐39−/−) mice.
YKL‐40 level was significantly increased in serum of AD patients. In addition, both mRNA and protein expression levels of BRP‐39 were higher in OVA‐sensitized WT mice than in control mice. OVA‐sensitized BRP‐39−/− mice showed decreased epidermal thickness, lower total serum IgE, Th2 cytokine levels and CD4+ effector T cell populations than OVA‐sensitized WT mice. Induction of BRP‐39 was dominant in dermal macrophages. BRP‐39 deficiency was found to be involved in M2 macrophage activation. Consistently, the YKL‐40 level in the skin of AD patients was higher than in normal subjects and it was expressed in dermal macrophages. BRP‐39 deficiency attenuated dysregulation of skin barrier and tight junction genes.
Conclusions and Clinical Relevance
These findings demonstrate that CHI3L1 mediates the development of AD induced by OVA, affecting Th2 inflammation, M2 macrophage activation and skin barrier function.
The role of mouse dermal γδ T cells in inflammatory skin disorders and host defense has been studied extensively. It is known that dendritic epidermal T cells (DETC) have a monomorphic γδ T cell ...receptor (TCR) and reside in murine epidermis from birth. We asked if dermal γδ cells freely re-circulated out of skin, or behaved more like dermal resident memory T cells (TRM) in mice. We found that, unlike epidermal γδ T cells (DETC), dermal γδ cells are not homogeneous with regard to TCR, express the tissue resident T cell markers CD69 and CD103, bear skin homing receptors, and produce IL-17 and IL-22. We created GFP+: GFP- parabiotic mice and found that dermal γδ T cells re-circulate very slowly-more rapidly than authentic αβ TCR TRM, but more slowly than the recently described dermal αβ TCR T migratory memory cells (TMM). Mice lacking the TCR δ gene (δ-/-) had a significant reduction of 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity (CHS). We created mice deficient in dermal γδ T cells but not DETC, and these mice also showed a markedly reduced CHS response after DNFB challenge. The infiltration of effector T cells during CHS was not reduced in dermal γδ T cell-deficient mice; however, infiltration of Gr-1+CD11b+ neutrophils, as well as ear swelling, was reduced significantly. We next depleted Gr-1+ neutrophils in vivo, and demonstrated that neutrophils are required for ear swelling, the accepted metric for a CHS response. Depletion of IL-17-producing dermal Vγ4+ cells and neutralization of IL-17 in vivo, respectively, also led to a significantly reduced CHS response and diminished neutrophil infiltration. Our findings here suggest that dermal γδ T cells have an intermediate phenotype of T cell residence, and play an important role in primary CHS through producing IL-17 to promote neutrophil infiltration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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