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It has long been known that keratinocytes influence cutaneous immunity through secretion of soluble factors. Exosomes, small membrane vesicles of endocytotic origin, have been implicated in intercellular communication processes such as the transfer of tumor cell antigens and the activation of recipient dendritic cells ( DC). However, little is known about immunomodulatory functions of keratinocyte-derived exosomes. To address this question, we analysed exosome secretion of the murine keratinocyte cell line MPEK under steady state as well as inflammatory conditions (+/− IFNγ). These exosomes were readily taken up by bone marrow-derived DC ( BMDC) in vitro resulting in a matured phenotype, as evidenced by increased CD40 expression as well as by the production of large amounts of IL-6, IL-10 and IL-12. When the transfer of antigen-specific information through exosomes was investigated, it was found that keratinocytes took up antigen (ovalbumin) and transferred it to their exosomes. However, these antigen-harbouring exosomes failed to induce antigen-specific T cell responses via BMDC. Together, this novel biological function suggests that keratinocytes are able to direct unspecific immune processes but do not elicit specific immune responses. [ABSTRACT FROM AUTHOR]

Cultured primary human keratinocytes were screened for their expression of various members of the toll-like receptor (TLR) family. Keratinocytes were found to constitutively express TLR1, TLR2, TLR3, TLR5, and TLR9 but not TLR4, TLR6, TLR7, TLR8, or TLR10 as shown by polymerase chain reaction analysis. The expression of the crucial receptor for signaling of staphylococcal compounds TLR2 was also confirmed by immunohistochemistry, in contrast to TLR4, which showed a negative staining pattern. Next, we analyzed the activation of the proinflammatory nuclear transcription factor κB by Staphylococcus aureus strain 8325-4. Using nuclear extract gel shifts, RelA staining, and luciferase reporter transfection plasmids we found a clear induction of nuclear factor κB translocation by the bacteria. This translocation induced the transcription of nuclear factor κB controlled genes such as inducible nitric oxide synthetase, COX2, and interleukin-8. Transcription of these genes was followed by production of increased amounts of interleukin-8 protein and NO. Inhibition experiments using monoclonal antibodies and the specific platelet activating factor receptor inhibitor CV3988 showed that nuclear factor κB activation by S. aureus was TLR2 but not TLR4 or platelet activating factor receptor dependent. In line, the purified staphylococcal cell wall components lipoteichoic acid and peptidoglycan, known to signal through TLR2, also showed nuclear factor κB translocation in human keratinocytes, indicating a crucial role of the staphylococcal cell wall in the innate immune stimulation of human keratinocytes. These results help to explain the complex activation of human keratinocytes by S. aureus and its cell wall components in various inflammatory disorders of the skin. [ABSTRACT FROM AUTHOR]

DNA sequences containing CpG have been described to induce a strong immune reaction by acting on a variety of immune cells including a strong and pronounced antitumoral response. Poly-G-oligodeoxynucleotides (ODNs) on the other hand have been attributed the preferential induction of CD8-T-cell proliferation when used in vitro. This activity led us to the investigation of the possible antitumoral properties of poly-G-ODNs in an established CD8-dependant tumor eradication model. We used the well described poly-G-ODN 1628 in its capacity to enhance antitumoral CD8 response in the cutaneous mastocytoma P815. When injecting 30 μg of the purified phosphothioate-modified oligo into the tumor bearing area of P815 challenged mice for up to 12 consecutive days we did not observe increased tumor rejection as compared to the group of mice injected with a control oligo. The 1628-injected mice did not produce higher numbers of P815-specific CD8 cells as measured by P1A-, and P1E-tetramer staining and Immunoscope analysis. Furthermore, tumor-specific CD8 cells in 1628 did not show enhanced antitumoral cytotoxicity when analyzing lymphocyte-tumor cell co-cultures or transcription of the cytotoxic CD8-cell associated molecules interferon γ, FAS ligand, perforin, or granzyme B by quantitative real-time RT-PCR. These experiments show that there is no enhanced induction of an antitumoral CD8 response after in situ administration of poly-G-ODNs in the P815 mastocytoma model. [Copyright &y& Elsevier]

Handling of Vaccinia virus represents a risk for laboratory-acquired infections, especially in individuals without completed vaccination. We report the case of a Vaccinia infection in a previously vaccinated researcher working with various genetically modified strains. We could confirm the infection by electron microscopy, positive cell culture, virus-specific PCR, sequence analysis, and viral neutralization test. The isolated virus carried a functionally inactivated cytohesin-1 gene of human origin, which had been shown to impair leukocyte adhesion by interacting with the LFA/ICAM-1 axis. The immunomodulating nature of the inserted construct might thus have added to the infectivity of the virus. We emphasize on the necessity of Vaccinia vaccination in laboratory staff working in the field. [ABSTRACT FROM AUTHOR]

Different mechanisms underlie the phenomenon of peripheral tolerance. Recently, a new subset of CD4+ T cells, called T regulatory-1 (Tr1) cells, was described which show suppressor functions in vitro and in vivo and are characterized by a predominant production of IL-10 and/or TGF-β. Tr1 cells have so far been generated experimentally in an IL-10-rich environment and hold promise for exploitation in the suppression of alloreactions and inflammatory or allergic dispositions. However, these cells have not been characterized in infectious diseases. Here we show that in the chronic helminth infection onchocerciasis (river blindness), where patients have relatively little sign of dermatitis despite the presence of millions of small worms in the skin, T cells can be obtained which bear characteristics of Tr1 cells, producing no IL-2 or IL-4 but substantial amounts of IL-10, variable amounts of IL-5, and some IFN-γ. These cells display elevated amounts of CTLA-4 after stimulation and are able to inhibit other T cells in coculture, in contrast to Th1 and Th2 clones. This is the first time that this type of suppressor T cell has been cloned as naturally occurring during an infectious disease. [Copyright &y& Elsevier]

Granuloma annulare is a common granulomatous infiltration of the skin of unknown etiopathogenesis. We analyzed granuloma annulare biopsies in 11 patients and could find in all patients significant numbers of CD4-T cells. These cells showed a broad usage of the different T cell receptor Vβ families and a rather unbiased repertoire when the complementary determining region 3 spectra were analyzed by the Immunoscope technique. Comparison with the peripheral blood mononuclear cell repertoire, however, identified in all patients few skin-specific expansions, which were for one patient also present in two distinct skin sites. Extensive sequence analysis of the complementary determining region 3 region confirmed the presence of a limited number of skin-specific expansions together with various nonspecific T cell infiltrations. Analysis of the intralesional cytokine expression revealed abundant production of interleukin-2, which was not dominant in granulomas from leprosy patients and was not reflected by the cytokine profile in peripheral blood mononuclear cells. These results demonstrate the capacity of the granulomatous response to recruit T cells in high numbers with only few clones expanding specifically. The high local production of interleukin-2 might thereby play an important role in the nonspecific attraction of T cells to the granulomatous site. [ABSTRACT FROM AUTHOR]

Colonization of human skin with Staphylococcus aureus is a common feature in a variety of dermatologic diseases. In order to reproducibly investigate the adherence of Staphylococcus aureus to human epidermal cells, an in vitro assay was established using the biotin/streptavidine labeling system and the HaCaT cell line. This assay was used to define the role of several Staphylococcus aureus surface proteins with regard to their function in the staphylococcal adhesion process. Our studies included the standard laboratory strain Newman as well as its genetically constructed mutants DU5873, DU5852, DU5854, and DU5886 generated by allele replacement or transposon mutagenesis, which are deficient in the elaboration of staphylococcal protein A (spa), clumping factor (clfA), coagulase (coa), and the fibronectin‐binding proteins A and B (fnbA/B), respectively. In comparison with strain Newman all mutants showed remarkably reduced adherence to the HaCaT keratinocyte cell line in our assay, yielding only between 43% and 60% of the adherence capacity of strain Newman after 60 min. Bacterial adherence could be re‐established by introducing the cloned wild‐type genes for the surface proteins on shuttle plasmids into the chromosomally defective mutants, thus suggesting a pathogenetic role of these proteins in the attachment of Staphylococcus aureus to human keratinocytes. Bacterial adherence was additionally enhanced by alkaline pH‐values that are characteristic for skin conditions with epidermal barrier dysfunction. The use of Staphylococcus aureus mutant strains, deficient in the elaboration of defined proteins, allows specific investigation of colonization and virulence factors of this dermatologic relevant microorganism. Key word: surface proteins. J Invest Dermatol 111:452–456 1998. [ABSTRACT FROM AUTHOR]

The article discusses the formation of an abdominal postoperative pyoderma gangrenosum (PPG), a rare and rapidly developing complication of surgical procedures, following a laparoscopic sigmoidectomy. It cites the case of a 39-year-old patient with a progressive ulceration at the lower abdomen that occurred after a laparoscopic sigmoid resection. Moreover, it examines the diagnosis of PPG.

Background: There exist several reports of atopy and allergen-specific IgE-mediated hypersensitivity transferred by bone marrow transplantation, and it has been concluded that the transfer of allergic reactivity results from adoptive transfer of IgE-producing donor-derived B- and/or plasma cells. To the best of our knowledge we report the first case of peanut allergy after PBSCT. Case Presentation: A 55-year-old anciently non allergic man with secondary acute myeloid leukemia (AML) received an allogeneic peripheral blood stem cell transplantation from a matched unrelated donor following reduced-intensity conditioning. On day 32 after PBSCT, while still on prophylactic systemic immunosuppression, the patient noticed a first episode of angioedema with swelling of the nasal and oral mucosa 30 min after consuming peanut puffs. In a second episode, eight months after PBSCT, he again developed angioedema, generalized pruritus and nausea within minutes after eating biscuits containing hazelnut and peanut. Moreover, after topical application of a peanut oil-containing ointment, the patient experienced facial erythema and angioedema. Nine months after PBSCT an evaluation for peanut allergy revealed a highly increased specific IgE to peanut of 75.9 kU/l. Accordingly, skin prick tests for peanut extract were also positive. In consequence, the patient was counseled to strictly avoid peanut-related products, and provided with an emergency set. No adverse allergic events have occurred since for an observation time of 15 months after PBSCT. The stem cell donor was contacted and confirmed intolerance to peanuts. His specific serum IgE pattern nine month after PBSCT harvest was analysed and showed similar sensitization profiles compared to those of the transplant recipient. Conclusions: Because of the close temporal association between the onset of allergic symptoms in the PBSC recipient it is reasonable to assume that the acquired peanut allergy had been transferred from the donor to the recipient by the PBSC graft. [ABSTRACT FROM AUTHOR]

Background: Studies on patch testing with workplace materials and evaluation of current occupational relevance of positive patch test reactions are scarce in patients with occupational dermatitis (OD). Objectives: To identify frequent sensitizations with occupational relevance and to determine the value of patch testing with workplace materials in OD patients. Patients and Methods: Results and clinical data of 654 patients with suspected OD patch tested between 2013 and 2017 were analysed. Results: Occupational allergic contact dermatitis was diagnosed in 113 (17.3%) patients. Mechanics had the widest range of occupational sensitizations. Sensitization to epoxy resin was rated occupationally relevant in almost all handicraft trades. Among positive patch test reactions to workplace products, those to water‐based metal working fluids and leave‐on cosmetic products were most frequent. Despite frequent testing, protective gloves only rarely elicited positive reactions. Preservatives and rubber compounds were most frequently identified as currently occupationally relevant. Conclusions: Rubber allergy is occupationally relevant especially in healthcare workers and cleaners. Generally, preservatives including formaldehyde releasers are important allergens in OD patients. Leave‐on cosmetic products must not be forgotten as allergen sources. Patch testing both workplace materials and standardized test preparations has a complementary value and is beneficial for the diagnostic work‐up of OD patients. Highlights: Patch testing of workplace materials and standardized test preparations has a complementary value in the diagnostic work‐up of occupational dermatitis patients.Mechanics should be patch tested in a broad fashion, including rubber, metal working fluids, epoxy resin systems, and leave‐on products.Epoxy resin systems exhibit current occupational relevance in almost all high‐risk professions of the handicraft sector. [ABSTRACT FROM AUTHOR]

Background: Metal work apprentices (MWAs) frequently develop work‐related hand eczema (HE). Objectives: To evaluate the effect of health education on incidence of work‐related HE in MWAs and to assess confounding factors. Materials/methods: In a prospective controlled intervention study, 131 MWAs received educational training on prevention of HE, whereas 172 MWAs and 118 office work apprentices served as controls. At baseline and during three yearly follow‐ups, questionnaires were completed and hands were examined. Saliva samples were collected for assessment of filaggrin (FLG) null mutations and an explorative genome‐wide association study (GWAS), and levels of various cytokines were assessed from stratum corneum samples. Results: The 2‐year and 3‐year incidence of HE in the metalwork control group was 20.9% and 32.6%, respectively, which was significantly higher than in the intervention group (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.31 to 5.28, P <.01 and OR 3.47, 95% CI 1.88 to 6.40, P <.0001). The knowledge score was higher in unaffected MWAs (P <.05). Other factors significantly associated with developing HE in MWAs were smoking cigarettes (P <.01) and FLG mutations (P <.001). No significant associations were found regarding epidermal cytokine levels and GWAS. Conclusions: Health education is effective in primary prevention of HE in MWAs. Individual factors should be considered in targeted counseling. [ABSTRACT FROM AUTHOR]

Background: Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss‐of‐function mutations of these genes constitute a risk factor for atopic dermatitis and eczema‐related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation. Methods: By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double‐deficient (FlgHrnr−/−) mouse model lacking both genes including the intergenomic sequence. Results: Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr−/− mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr−/− mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Surprisingly, although the immune system revealed no aberrations under steady‐state conditions, FlgHrnr−/− mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions. Conclusions: Together, our FlgHrnr−/− mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions. [ABSTRACT FROM AUTHOR]

Lyme borreliosis is a common infectious disease that can affect myocardial muscle or the central nervous system if not treated at an early stage. Here we report a unique case of an atypical location of lymphocytoma cutis in a 3-year-old boy. Histologic and immunohistochemical analysis revealed the correct diagnosis. [ABSTRACT FROM AUTHOR]

Patients with atopic dermatitis (AD) tend to have greatly elevated levels of serum immunoglobulin E (IgE). However, the role of IgE in the pathogenesis of AD is debated. This investigator-initiated open-label pilot study evaluates an anti-IgE-treatment approach by combining extracorporeal immunoadsorption and anti-IgE antibody omalizumab in 10 patients with severe, therapy-refractory AD. IgE levels decreased after immunoadsorption and decreased continuously in all patients during anti- IgE therapy. The reverse trend was observed during 6 months follow-up without treatment. In parallel with these observations, an improvement in AD was observed during the treatment period, with aggravation during follow-up. Further research is needed, based on the principle of reducing IgE levels in order to improve clinical symptoms, using a combination anti-IgE treatment approach, adjusted according to IgE levels. [ABSTRACT FROM AUTHOR]

Psoriasis is characterized by an apoptosis-resistant and metabolic active epidermis, while a hallmark for allergic contact dermatitis (ACD) is T cell-induced keratinocyte apoptosis. Here, we induced ACD reactions in psoriasis patients sensitized to nickel (n = 14) to investigate underlying mechanisms of psoriasis and ACD simultaneously. All patients developed a clinically and histologically typical dermatitis upon nickel challenge even in close proximity to pre-existing psoriasis plaques. However, the ACD reaction was delayed as compared to non-psoriatic patients, with a maximum intensity after 7 days. Whole genome expression analysis revealed alterations in numerous pathways related to metabolism and proliferation in non-involved skin of psoriasis patients as compared to non-psoriatic individuals, indicating that even in clinically non-involved skin of psoriasis patients molecular events opposing contact dermatitis may occur. Immunohistochemical comparison of ACD reactions as well as in vitro secretion analysis of lesional T cells showed a higher Th17 and neutrophilic migration as well as epidermal proliferation in psoriasis, while ACD reactions were dominated by cytotoxic CD8+ T cells and a Th2 signature. Based on these findings, we hypothesized an ACD reaction directly on top of a pre-existing psoriasis plaque might influence the clinical course of psoriasis. We observed a strong clinical inflammation with a mixed psoriasis and eczema phenotype in histology. Surprisingly, the initial psoriasis plaque was unaltered after self-limitation of the ACD reaction. We conclude that sensitized psoriasis patients develop a typical, but delayed ACD reaction which might be relevant for patch test evaluation in clinical practice. Psoriasis and ACD are driven by distinct and independent immune mechanisms. [ABSTRACT FROM AUTHOR]

Optimized delivery of antigens combined with sustainable maturation of dendritic cells ( DCs) is crucial for generation of effective antitumoral immune responses. Multiple approaches for ex vivo antigen loading and improvement in immunogenicity have been described. We have recently established a single-step protocol consisting of a fusion peptide (a sequence of the melanoma antigen Melan- A and a cationic cell-penetrating HIV TAT domain) bound in complexes with a toll-like receptor agonist. As the exact cellular uptake mechanisms of TAT-coupled antigens have been a matter of considerable debate and significantly depend on cell type, cargo and concentrations, we evaluated internalization routes into human immature DCs in comparison with non-phagocytic cell lines. We found that Melan- A- TAT fusion peptide uptake by DCs is mainly energy dependent, superior compared with polylysine-coupled Melan- A and significantly higher in DCs as compared with Jurkat cells or HUVECs. Furthermore, we could track the uptake of the fusion peptide exclusively through early endosomes to lysosome compartments after 90 min by fluorescence microscopy and immunoelectron microscopy. Specific endocytosis inhibitors revealed major internalization of the fusion peptide by DCs via clathrin-mediated endocytosis, whereas uptake by non-phagocytic HUVECs differed significantly, involving macropinocytosis as well as clathrin-mediated endocytosis. As our understanding of the processes involved in internalization of TAT-coupled cargos by human DCs broadens, and DC activation becomes available by single-step procedures as described, further development of simultaneous DC maturation and intra-cellular peptide targeting is warranted. [ABSTRACT FROM AUTHOR]

: The simultaneous occurrence of psoriasis driven by type 1 helper T (Th1) cells and type 17 helper T (Th17) cells and atopic eczema dominated by type 2 helper T (Th2) cells is rare. Here, we describe three patients with co-occurring psoriasis and atopic eczema with an antagonistic course and distinct T-cell infiltrates in lesions from psoriasis and those from atopic eczema. Sensitized patients with psoriasis had a reaction to epicutaneous allergen challenge, with clinically and histologically verified eczema lesions containing a large number of allergen-reactive T cells. These findings support a causative role for T cells triggered by specific antigens in both psoriasis and atopic eczema. (Supported by the German Research Foundation and others.) [ABSTRACT FROM PUBLISHER]

Abstract: Anti-IgE therapeutics represent an efficient approach in the management of IgE-mediated allergic asthma. However, monitoring the reduction of IgE levels into a therapeutically efficient range requires the determination of residual serum IgE. We established an analytical approach to distinguish free and anti-IgE complexed serum IgE based on soluble derivatives of the human high-affinity IgE receptor. Soluble receptor derivatives represent an ideal means to analyze receptor antagonism by any ligand or blocking antibody. Therefore, the FcεRI ectodomain was fused with avian IgY constant domains that circumvent susceptibility to interference phenomena and improve assay performance. After production in HEK293 cells, subsequent characterization by enzyme-linked immunosorbent assay and immunoblotting confirmed the suitability of avian IgY constant domains for immobilization and detection purposes. To provide further insights into the different IgE reactivities, free allergen-specific IgE was also determined. Monitoring of sera from omalizumab-treated patients during the course of therapy revealed the applicability for assessment of omalizumab-complexed versus noncomplexed serum IgE. These parameters may allow correlation to clinical responses during anti-IgE therapy with the perspective of biomonitoring. [Copyright &y& Elsevier]

Abstract: The endocannabinoid system (ECS) consists of two cannabinoid (CB) receptors, namely CB1 and CB2 receptor, and their endogenous (endocannabinoids) and exogenous (cannabinoids, e.g. delta-9-tetrahydrocannabinol (THC)) ligands which bind to these receptors. Based on studies suggesting a role of THC and the ECS in inflammation, the objective of this study was to examine their involvement in type I hypersensitivity using a murine model of allergic airway inflammation. THC treatment of C57BL/6 wildtype mice dramatically reduced airway inflammation as determined by significantly reduced total cell counts in bronchoalveolar lavage (BAL). These effects were greatest when mice were treated during both, the sensitization and the challenge phase. Furthermore, systemic immune responses were significantly suppressed in mice which received THC during sensitization phase. To investigate a role of CB1/2 receptors in this setting, we used pharmacological blockade of CB1 and/or CB2 receptors by the selective antagonists and moreover CB1/CB2 receptor double-knockout mice (CB1 −/−/CB2 −/−) and found neither significant changes in the cell patterns in BAL nor in immunoglobulin levels as compared to wildtype mice. Our results indicate that the activation of the ECS by applying the agonist THC is involved in the development of type I allergies. However, CB1/CB2 receptor-independent signalling seems likely in the observed results. [Copyright &y& Elsevier]

Primary human keratinocytes and immortalized HaCaT cells were analysed for their capacity to bind purified staphylococcal protein A (SpA). Co-incubation with FITC-labelled SpA led to a dose-depending attachment. Pull-down experiments with cellular extracts revealed the TNFα receptor I (TNF RI) as binding partner on keratinocytes. Thus, we next looked for expression of this receptor in human epidermis and cultured keratinocytes. TNF RI is strongly expressed on all keratinocytes analysed, both at the mRNA and protein level and activation by SpA at optimal doses of 50-100 μg/ml resulted in the phosphorylation of the TNF RI downstream kinases MEK1/2, JNK1/2, and p38 subsequently leading to translocation of the p65 NF kappa B subunit and AP-1 into the nucleus. This translocation was then followed by increased expression of IL-8 and COX-2, two known NF kappa B-induced pro-inflammatory genes. To further test the relevance of our findings, we analysed in vitro production of over 100 strains isolated from atopic eczema showing that more than 85% of the tested strains produced extracellular SpA in substantial amounts. Thus, besides superantigens, haemolysins, and other cell wall components, Staphylococcus aureus exerts pro-inflammatory stimuli on human keratinocytes through the production of SpA signalling through TNF RI. [ABSTRACT FROM AUTHOR]

The family of toll-like receptors (TLRs) plays a central role in the cutaneous immune defense system. To date, different TLRs have been found on several major cell populations of the skin, such as keratinocytes, fibroblasts, antigen-presenting cells, and melanocytes. Activation of TLRs leads, via different intracellular signaling pathways, to the production of proinflammatory stimuli, and is considered a danger signal that should transform the skin in to the functional state of defense. However, TLRs have also been implicated in tissue homeostasis and renewal. Within the group of TLRs, two types have been identified: surface-expressed TLRs, which are predominantly active against bacterial cell wall compounds; and intracellular receptors, which preferentially recognize virus-associated pattern molecules. In addition, surface-expressed receptors trigger phagocytotic and maturation signals, while the intracellular TLRs lead to the induction of antiviral genes. Our review aims to outline the importance of TLRs in the pathogenesis of numerous skin diseases and the potential of TLR agonists as a treatment option for various skin diseases. [ABSTRACT FROM AUTHOR]

Diesel exhaust particles (DEP) were described as potent adjuvant in the induction and maintenance of allergic diseases, suggesting that they might play a role in the increase of allergic diseases in the industrialized countries. However, the cellular basis by which these particles enhance allergic immune responses is still a matter of debate. Thus, we exposed immature murine bone marrow–derived dendritic cells (BMDC) to different particles or particle-associated organic compounds in the absence or presence of the maturation stimuli lipopolysaccharide (LPS) and analyzed the cellular maturation, viability, and cytokine production. Furthermore, we monitored the functionality of particle-exposed BMDC to suppress B cell isotype switching to immunoglobulin (Ig) E. Only highly polluted DEP (standard reference material 1650a [SRM1650a]) but not particle-associated organic compounds or less polluted DEP from modern diesel engines were able to modulate the dendritic cell phenotype. SRM1650a particles significantly suppressed LPS-induced IL-12p70 production in murine BMDC, whereas cell-surface marker expression was not altered. Furthermore, SRM1650a-exposed immature BMDC lost the ability to suppress IgE isotype switch in B cells. This study revealed that highly polluted DEP not only interfere with dendritic cell maturation but also additionally with dendritic cell function, thus suggesting a role in Th2 immune deviation. [ABSTRACT FROM PUBLISHER]

High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85×10-20 and 7.08×10-19 in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78×10-4 and P = 1.95×10-3). The ''top'' SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28610-724.46×10-8) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels. [ABSTRACT FROM AUTHOR]

Background: Regulatory T cells (T-reg cells) have been described as an important cell population in the UV treatment of inflammatory skin diseases. Methods: We have treated five patients with generalized atopic eczema (AE) using medium-dose (15 cycles of 50 J/cm2, total dose of 750 J/cm2) UVA1 therapy and have analyzed the skin-infiltrating T-cellular subsets before and after therapy. Skin biopsies were split for immunohistochemistry and Real-time PCR and analyzed for CD4, Fox-P3, GATA-3, and IL-10 transcription as well as for CD3, CD4, CD152, Fox-P3, and GITR staining. Results: In all the investigated patients, we observed a good clinical response to UVA1. As described previously, the number of epidermal T cells slightly declined after irradiation. However, we did not observe a general decrease in T cell numbers. Within the population of T cells, no specific difference in the kinetics of Fox-P3-positive cells and Fox-P3-specific mRNA was noted as compared with GATA-3 positive T cells. These results were paralleled by RT-PCR for IL-10 and staining for CD152, a surface molecule that has been described for T-reg cells. Conclusion: In our hands, the clinical benefit of UVA1 treatment in AE patients does not seem to be due to a preferential survival/proliferation of T-reg cells. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are important pattern recognition molecules that activate the nuclear factor (NF)-κB pathway leading to the production of antimicrobial immune mediators. As keratinocytes represent the first barrier against exogenous pathogens in human skin, we investigated their complete functional TLR1–10 expression profile. First, reverse transcription–polymerase chain reaction (PCR) analysis revealed a very similar pattern of TLR mRNA expression when comparing freshly isolated human epidermis and cultured primary human keratinocytes. Thus, further experiments were carried out with primary keratinocytes in comparison with the spontaneously immortalized human keratinocyte cell line HaCaT. The quantitative expression of TLR1–10 mRNA in real-time PCR of primary human keratinocytes and HaCaT cells was analysed. Both cell types constitutively expressed TLR2, TLR3, TLR5, and to a lesser extent TLR10. TLR4 was only found in HaCaT cells, TLR1 to a higher degree in primary keratinocytes. In line with this, LPS induced mRNA expression of CD14 and TLR4 only in HaCaT cells. After stimulation with various TLR ligands, the NF-κB-activated chemokine interleukin-8 (IL-8) was measured. In primary keratinocytes and HaCaT cells the TLR3 ligand poly (I:C) was the most potent stimulator of IL-8 secretion. The TLR ligands peptidoglycan, Pam3Cys and flagellin which bind to TLR2, TLR1/TLR2 heterodimer, and TLR5, respectively, also induced IL-8 secretion, whereas no IL-8 was induced by LPS, R-848, loxoribine and cytosine guanine dinucleotide-containing oligodeoxynucleotide. A corresponding pattern was found in the RelA NF-κB translocation assay after ligand stimulation of primary keratinocytes. These studies provide substantial evidence for a functional TLR expression and signalling profile of normal human keratinocytes contributing to the antimicrobial defence barrier of human skin. [ABSTRACT FROM AUTHOR]

The article presents a case study of an eight-month-old white girl with phacomatosis cesiomarmorata. She was diagnosed of having cutaneous vascular and pigmentary abnormalities which were held since birth. Furthermore, physical examination has discovered that reddish-blue reticulated lesions were designated in a homogenous pattern on extremities. A discussion on the classification of phacomatosis pigmentovascularis (PPV) is provided.

An answer to a photo quiz related to the diagnosis of ulcerative mucositis, skin lesions, and nail dystrophy in a 32 year old man published in the periodical is presented.

Background: A type-IV-allergic reaction to German camomile (Matricaria chamomilla) in a form of allergic contact dermatitis is not unusual. However, only a few cases of anaphylactic reaction to camomile have been described in the literature. Case Summary: We present the case of a 38-year-old Caucasian man who developed an episode of severe anaphylaxis with generalized urticaria, angioedema and severe dyspnoea one hour after consuming camomile tea. Laboratory examination demonstrated a total serum IgE of 123 kU/I with specific IgE against camomile (4.94 kU/I, class 3). Skin prick test and labial provocation test with camomile showed a strong positive reaction. Discussion: Our case confirms the presence of a type-I allergy to orally ingested camomile and indicates that the incidence and risk may be underestimated. Additional response to mugwort and pollen-derived food allergens should be evaluated in patients sensitised to camomile due to a higher incidence of allergic cross-reactivity. [ABSTRACT FROM AUTHOR]

Investigates the efficacy of local UVA1 irradiations in the treatment of chronic vesicular dyshidrotic hand eczema. Exposure of palms and back of hands to 15 UVA1 irradiations; Improvement of dyshidrotic hand eczema; Absence of relapse during post-treatment intervals.