The relationship between serum levels of total IgE, IL-18, IL-12, IFN-gamma and disease severity in children with atopic dermatitis

Studies about the role of cytokines on the immunopathogenesis of atopic dermatitis (AD) are generally based on in vitro observations and this role has not been completely clarified yet. Serum levels of total IgE, IL-18, IL-12, IFN-gamma and the relationship between these parameters and disease severity, determined using the SCORAD index, in a group of atopic patients were investigated in this study. Serum levels of total IgE were measured by the nephelometric method and serum levels of IL-18, IL-12/p40 and IFN-gamma were measured by ELISA method. Serum levels of total IgE and IL-18 were found significantly higher in study group than in controls (P<.001). There was no statistically significant difference between patients and controls in respect of serum levels of IL-12/p40 (P = .227). A statistically significant relationship between SCORAD values and serum levels of total IgE (P < .001), IL-18 (P < .001), and IL-12/p40 (P < .001) was determined. These results show that serum levels of IL-18 can be a sensitive parameter that importantly correlates with clinical severity of AD, can play a role in the immunopathogenesis of AD, and furthermore may be used in the diagnosis and follow-up of the disease in addition to other parameters.     

Role of Macrophage Migration Inhibitory Factor (MIF) in Pollen-Induced Allergic Conjunctivitis and Pollen Dermatitis in Mice

Pollen is a clinically important airborne allergen and one of the major causes of allergic conjunctivitis. A subpopulation of patients with atopic dermatitis (AD) are also known to have exacerbated skin eruptions on the face, especially around the eyelids, after contact with pollen. This pollen-induced skin reaction is now known as pollen dermatitis. Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine that plays an essential role in allergic inflammation. Recent findings suggest that MIF is involved in several allergic disorders, including AD. In this study, MIF knockout (KO), MIF transgenic (Tg) and WT littermate mice were immunized with ragweed (RW) pollen or Japanese cedar (JC) pollen and challenged via eye drops. We observed that the numbers of conjunctiva- and eyelid-infiltrating eosinophils were significantly increased in RW and JC pollen-sensitized MIF Tg compared with WT mice or MIF KO mice. The mRNA expression levels of eotaxin, interleukin (IL)-5 and IL-13 were increased in pollen-sensitized eyelid skin sites of MIF Tg mice. An in vitro analysis revealed that high eotaxin expression was induced in dermal fibroblasts by MIF combined with stimulation of IL-4 or IL-13. This eotaxin expression was inhibited by the treatment with CD74 siRNA in fibroblasts. These findings indicate that MIF can induce eosinophil accumulation in the conjunctiva and eyelid dermis exposed to pollen. Therefore, targeted inhibition of MIF might result as a new option to control pollen-induced allergic conjunctivitis and pollen dermatitis.     

7,8,4′-Trihydroxyisoflavone Attenuates DNCB-Induced Atopic Dermatitis-Like Symptoms in NC/Nga Mice

Atopic dermatitis (AD) is characterized by chronic highly pruritic and relapsing inflammatory skin lesions. Despite its growing prevalence, therapeutic treatments remain limited. Natural immune modulators from herbal extracts or derivatives may be useful for treating AD symptoms. This study examined the effect of 7,8,4′-trihydroxyisoflavone (7,8,4′-THIF), a metabolite of soy isoflavone daidzin, on AD-like symptoms. Repeated epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) was performed on the ear and dorsal skin of NC/Nga mice to induce AD-like symptoms and skin lesions, and 7,8,4′-THIF (200 and 400 nmol) or tacrolimus (100 µg) was applied topically for 3 weeks to assess their anti-pruritic effects. We found that 7,8,4′-THIF alleviated DNCB-induced AD-like symptoms as quantified by skin lesion, dermatitis score, ear thickness, and scratching behavior. Histopathological analysis demonstrated that 7,8,4′-THIF decreased DNCB-induced eosinophil and mast cell infiltration into skin lesions. We also found that 7,8,4′-THIF significantly alleviated DNCB-induced loss of water through the epidermal layer. In addition to reducing the DNCB-induced increase in serum IgE, 7,8,4′-THIF also lowered skin lesion levels of the chemokine thymus and activation regulated chemokine; Th2 cytokines interleukin (IL)-4, IL-5, and IL-13; and Th1 cytokines IL-12 and interferon-γ. These results suggest that 7,8,4′-THIF might be a potential therapeutic candidate for the treatment of atopic dermatitis.     

Genuine traditional Korean medicine,Naju Jjok (Chung-Dae,Polygonum tinctorium) improves 2,4-dinitrofluorobenzene-induced atopic dermatitis-like lesional skin

PurposeNaju Jjok (NJJ, Polygonum tinctorium) is a clear heat and release toxin medicinal. It has been used to treat various inflammatory diseases and as a dye in clothing in traditional Korean medicine. However, the effect of NJJ on atopic dermatitis (AD) has not been elucidated. Therefore, we examined whether NJJ would have an inhibitory effect on AD using the mimic AD murine model and in vitro model.MethodsWe treated NJJ on 2,4-dinitrofluorobenzene (DNFB)-induced AD-like skin lesions in NC/Nga mice, phorbol myristate acetate/calcium ionophore A23187-stimulated human mast cell line (HMC-1) cells, and anti-CD3/anti-CD28-stimulated splenocytes. Histological analysis, ELISA, PCR, and Western blot analysis were performed.ResultsThe oral administration with NJJ suppressed the total clinical severity in DNFB-induced AD-like lesional skin. NJJ significantly suppressed the levels of inflammatory mRNA and protein in AD-like lesional skin. NJJ significantly suppressed the levels of IgE and interleukin-4 in the serum of DNFB-induced AD mice. The expression of mast cells-derived caspase-1 was suppressed by NJJ in AD-like lesional skin. In addition, topical application with NJJ improved clinical symptoms in DNFB-induced AD mice. The topical application with NJJ significantly suppressed the levels of IgE and histamine in the serum of DNFB-induced AD mice. NJJ suppressed the production and mRNA expression of TSLP by blockade of caspase-1 signal pathway in the activated HMC-1 cells. Furthermore, NJJ significantly decreased the production of tumor necrosis factor-α from the stimulated splenocytes.ConclusionsIn conclusion, these results propose curative potential of natural dye, NJJ by showing the scientific evidence on anti-AD effect of NJJ which has been used traditionally.     

Engagement of the Fc epsilon RI stimulates the production of IL-16 in Langerhans cell-like dendritic cells.

Preferential uptake and presentation of IgE-bound allergens by epidermal Langerhans cells (LC) via the high affinity IgE receptor, FcepsilonRI, is regarded as an important mechanism in the induction of cutaneous inflammation in atopic dermatitis. Here, we show that activation of monocyte-derived LC-like dendritic cells (LLDC) through engagement of FcepsilonRI induces the expression of IL-16, a chemoattractant factor for dendritic cells, CD4+ T cells, and eosinophils. We found that ligation of FcepsilonRI on LLDC derived from atopic dermatitis patients that express high levels of FcepsilonRI increases IL-16 mRNA expression and storage of intracellular IL-16 protein and enhances the secretion of mature IL-16 in a biphasic manner. An early release of IL-16 (peak at 4 h) is independent of protein synthesis, while a more delayed release (peak at 12 h) requires protein synthesis and occurs subsequent to the induction of IL-16 mRNA and intracellular accumulation of pro-IL-16. There was evidence that LLDC use caspase-1 to process IL-16, as inhibition of caspase-1, but not of caspase-3, partially prevented the release of IL-16 in response to ligation of FcepsilonRI. In an in vivo model of IgE-dependent LC activation, the atopy patch test, positive skin reactions were also associated with the induction of IL-16 in epidermal dendritic cells. These data indicate that IL-16 released from LC after allergen-mediated activation through FcepsilonRI may link IgE-driven and cellular inflammatory responses in diseases such as atopic dermatitis.     

Development of atopic dermatitis-like skin lesions in STAT6-deficient NC/Nga mice

Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by elevation of plasma levels of total IgE, infiltration of mast cells and eosinophils, and the expression of cytokines by Th2 T cells. However, the role of Th2 cells in the pathogenesis of AD is not fully understood. In this study we examined the NC/Nga (NC) mouse model of AD and established STAT6-deficient (SATA6(-/-)) NC mice to investigate the relevance of IL-4-mediated immune responses. Surprisingly, these mice elicited AD-like skin lesions at equivalent frequency and time of onset compared with normal NC littermates. Histological features of the lesion in STAT6(-/-) NC mice fulfilled the criteria for the pathogenesis of AD, although these mice fail to produce IgE and Th2 cytokines. The lymph nodes proximal to the regions of skin that developed lesions exhibited massive enlargement elicited by the accumulation of activated IFN-gamma-secreting T cells. Moreover, caspase I, IL-18, IL-12, and IFN-gamma are found to be highly expressed at the skin lesion, occurring simultaneously with elevation of eotaxin 2 and CCR3 expression. Therefore, the Th2-mediated immune response is not necessary for the development of AD-like skin disease in NC mice. The skin microenvironment that favored IFN-gamma production tightly correlates with the skin disease in NC mice through the infiltration of eosinophils.     

Topical superantigen exposure induces epidermal accumulation of CD8+ T cells, a mixed Th1/Th2-type dermatitis and vigorous production of IgE antibodies in the murine model of atopic dermatitis

Patients with atopic dermatitis (AD) have repeated cutaneous exposure to both environmental allergens and superantigen-producing strains of Staphylococcus aureus. We used a murine model of AD to investigate the role of staphylococcal enterotoxin B (SEB) in the modulation of allergen-induced skin inflammation. Mice were topically exposed to SEB, OVA, a combination of OVA and SEB (OVA/SEB), or PBS. Topical SEB and OVA/SEB exposure induced epidermal accumulation of CD8+ T cells and TCRVbeta8+ cells in contrast to OVA application, which induced a mainly dermal infiltration of CD4+ cells. SEB and OVA/SEB exposure elicited a mixed Th1/Th2-associated cytokine and chemokine expression profile within the skin. Restimulation of lymph node cells from OVA- and OVA/SEB-exposed mice with OVA elicited strong production of IL-13 protein, whereas substantial amounts of IFN-gamma protein were detected after SEB stimulation of cells derived from SEB- or OVA/SEB-exposed mice. Topical SEB treatment elicited vigorous production of SEB-specific IgE and IgG2a Abs and significantly increased the production of OVA-specific IgE and IgG2a Abs. The present study shows that topical exposure to SEB provokes epidermal accumulation of CD8+ T cells, a mixed Th2/Th1 type dermatitis and vigorous production of specific IgE and IgG2a Abs, which can be related to the chronic phase of atopic skin inflammation.     

Silkworm dropping extract ameliorate trimellitic anhydride-induced allergic contact dermatitis by regulating Th1/Th2 immune response

Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by hapten-specific immune response. Silkworm droppings are known to exert beneficial effects during the treatment of inflammatory diseases. Here, we studied whether topical treatment and oral administration of silkworm dropping extract (SDE) ameliorate trimellitic anhydride (TMA)-induced ACD. In ACD mice model, SDE treatment significantly suppressed the increase in both ear thickness and serum IgE levels. Furthermore, IL-1β and TNF-α levels were reduced by SDE. In allergic responses, SDE treatment significantly attenuated the production of the Th2-associated cytokine IL-4 in both ear tissue and draining lymph nodes. However, it increased the production of the Th1-mediated cytokine IL-12. Thus, these results showed that SDE attenuated TMA-induced ACD symptoms through regulation of Th1/Th2 immune response. Taken together, we suggest that SDE treatment might be a potential agent in the prevention or therapy of Th2-mediated inflammatory skin diseases such as ACD and atopic dermatitis.

Abbreviations: ACD: allergic contact dermatitis; AD: atopic dermatitis; APC: antigen presenting cells; CCL: chemokine (C-C motif) ligand; CCR: C-C chemokine receptor; Dex: dexamethasone; ELISA: enzyme-linked immunosorbent assay; IFN: interferon; Ig: immunoglobulin; IL: interleukin; OVA: ovalbumin; PS: prednisolone; SDE: silkworm dropping extract; Th: T helper; TMA: trimellitic anhydride; TNF: tumor necrosis factor     

Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-κB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1

PurposeThe consequences of precipitously rising allergic skin inflammation rates worldwide have accelerated the risk of atopic dermatitis (AD). Natural product-based agents with good efficacy and low risk of side effects offer promising prevention and treatment strategies for inflammation-related diseases. We have already reported that Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) have many pharmacological effects, including anti-inflammatory and anti-allergic effects, but its influence on AD remains unclear. Therefore, we evaluated the inhibitory effect of CKS, mainly platycodin D, on AD-like skin symptoms in mice and the possible mechanisms in cells.MethodsMice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB). Four weeks after challenge, mice were treated with oral administration of CKS for 4 weeks. In addition, cells were used to evaluate the effect of CKS, mainly platycodin D, on the TARC expression regulated mechanism.ResultsCKS attenuated DNCB-induced dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC, TNF-α, IFN-γ, IL-4, IL-5, and IL-13 in mice. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells and mast cells in the ears. Moreover, CKS and platycodin D inhibited TNF-α/IFN-γ-induced TARC expression through the suppression of NF-κB and STAT1 and induction of Nrf2/ARE-mediated hemeoxygenase-1 (HO-1) expression in cells.ConclusionWe suggest that CKS and platycodin D inhibited the development of AD-like skin symptoms by regulating cytokine mediators and may be an effective alternative therapy for AD-like skin symptoms.     

DNCB致敏/激发Nc/Nga小鼠特应性皮炎模型的建立

目的研究外用2,4-二硝基氯苯（DNCB）对Nc/Nga小鼠的致敏作用,探索建立特应性皮炎（AD）模型的方法。方法外用1%DNCB7周,间隔为1周,重复刺激并致敏7周大NC/Nga小鼠的双侧耳朵及背部皮肤。结果外用DNCB7周可以引起显著的炎症,并伴有高滴度的IgE和IL-4,利用HE染色进行组织病理分析,提示表皮炎性细胞明显增加。结论外用DNCB重复刺激Nc/Nga小鼠能产生AD样皮炎,可以作为研究AD病因及治疗AD的有效动物模型。     

Inhibitory effects of polysaccharide-rich extract of Phragmites rhizoma on atopic dermatitis-like skin lesions in NC/Nga mice

AimsPhragmites rhizoma was reported to have anti-oxidative and free radical scavenging activity. It also has been traditionally used to suppress inflammation. In the present study, we aimed to evaluate the topical effects of the polysaccharide-rich extract of P. rhizoma (PEP) on atopic dermatitis.Main methodsWe induced AD-like skin lesions by an extract of the house-dust mite Dermatophagoides farinae (Dfb) in NC/Nga mice, and then performed macroscopic analysis, immunohistochemical staining and measurement of total serum IgE and cytokine production by ELISA.Key findingsTopically applied PEP suppressed dermatitis with a decrease in dermatitis score and scratch number. The histological manifestations of atopic skin lesions including thickened epidermis and increased numbers of mast cells, polymorphonuclear leukocytes and nerve fibers were significantly attenuated. The activation of IgE and the levels of cytokines such as IFN-γ IL-4 and IL-10 were also decreased.SignificanceOur results indicated that PEP might have an inhibitory effect on atopic dermatitis-like lesion and be a promising natural resource in the treatment of atopic dermatitis.     

Arjunolic acid protects against DNCB-induced atopic dermatitis-like symptoms in mice by restoring a normal cytokine balance

Purpose

Atopic dermatitis (AD) is a chronically relapsing, pruritic, eczematous skin disorder accompanying allergic inflammation. AD is triggered by oxidative stress and immune imbalance. The effect of oral arjunolic acid (AA) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice was investigated.

Methods

Repeated epicutaneous application of DNCB to the ear and shaved dorsal skin of mice was performed to induce AD-like symptoms and skin lesions: 250mg/kg AA was given orally for three weeks to assess its anti-pruritic effects. Serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, immunoglobulin (Ig)E and caspase-3 were assessed by ELISA.

Results

We found that AA alleviated DNCB-induced AD-like symptoms as quantified by skin lesions, dermatitis score, ear thickness and scratching behavior. Levels of reactive oxygen species in the AA group were significantly inhibited compared with those in the DNCB group. In parallel, AA blocked a DNCBinduced reduction in serum levels of IL-4 and IL-10 associated with an attenuation of DNCB-induced increases in serum TNF-α, IL-6, IgE and caspase-3.

Conclusions

The results indicate that AA suppresses DNCB-induced AD in mice via redox balance and immune modulation, and could be a safe clinical treatment for AD.

     

Decreased IL-15 may contribute to elevated IgE and acute inflammation in atopic dermatitis.

PBMC and acute skin lesions of patients with atopic dermatitis (AD) are characterized by increased IL-4 and IL-13, but decreased IFN-gamma production. This bias toward an increased Th2 cytokine profile may contribute to the elevated IgE levels and acute skin inflammation seen in AD. In this study, we examined the levels of IL-15, a Th1-like cytokine, in the PBMC and the skin lesions of AD patients. IL-15 secretion by Staphylococcal enterotoxin B-treated PBMC of AD patients was significantly lower than that of normals and psoriasis patients (p < 0.001). Membrane-bound IL-15 expression as measured by mean fluorescence intensity and percentage of IL-15-positive cells in Staphylococcal enterotoxin B-treated monocytes of AD patients (644 +/- 49% and 12.7 +/- 0.6%, respectively) were significantly lower than that of normals (869 +/- 56% and 15.8 +/- 1.2%, respectively) and psoriasis patients (1488 +/- 217% and 22.7 +/- 0.8%, respectively; p < 0.0007 and p < 0.0001, respectively). The membrane-bound IL-15 expression was also significantly lower in the control monocytes of AD patients compared with that in normals and psoriasis patients. There was no significant difference in the absolute number or percentage of monocytes between the study subjects. However, psoriasis skin lesions were found to have significantly more IL-15 mRNA-expressing cells (22.4 +/- 1.7) compared with that in acute AD (7.5 +/- 1.7) and chronic AD (13.7 +/- 1.7) skin lesions (p < 0.05). IL-15 enhanced IFN-gamma production by the PBMC of AD patients (p < 0.01), but not by that of normal individuals or psoriasis patients. In addition, IL-15 was found to suppress IgE synthesis (p < 0.01) by the PBMC of AD patients. These data support the concept that reduced IL-15 expression may contribute to the pathogenesis of AD.     

Successful interferon alpha therapy in atopic dermatitis of Besnier's prurigo pattern with normal serum IgE and blood eosinophil fraction: randomized case-controlled study

A randomized case-controlled study was carried out to investigate for interferon alpha therapy in atopic dermatitis (AD) of Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. Interferon alpha therapy was conducted on 14 non-responders to interferon gamma and subsequent thymopentin therapy among 100 atopic dermatitis patients. Eight patients who improved significantly, showed skin lesions of the Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. For the randomized prospective case-controlled study, 44 patients with the above characteristics were selected. Thirteen Besnier's prurigo patients were treated with interferon alpha therapy, ten with interferon gamma, ten with thymopentin, and the remaining 11 were untreated as the control group. With interferon alpha therapy, 11 out of 13 Besnier's prurigo patients with normal IgE and normal blood eosinophil fraction improved significantly, two out of ten improved with interferon gamma therapy, and none improved with thymopentin therapy or in the untreated control group. Interferon alpha therapy was effective on AD of Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. These results suggest the possibility of non-IgE-mediated AD and the heterogeneity of atopic dermatitis.     

A combination of Olea europaea leaf extract and Spirodela polyrhiza extract alleviates atopic dermatitis by modulating immune balance and skin barrier function in a 1-chloro-2,4-dinitrobenzene-induced murine model

BackgroundAtopic dermatitis is a chronic inflammatory skin disease in humans. Although Olea europaea leaf extract (OLE) and Spirodela polyrhiza extract (SPE) have been used to protect against skin damage, the effects of their combined administration on atopic dermatitis have yet to studied.PurposeIn this study, we evaluated the potential therapeutic effects of an OLE and SPE combination on the progression of atopic dermatitis and the possible mechanisms underlying these effects in 1-chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice.MethodsAtopic dermatitis was induced by topical application of 0.2% w/v DNCB prepared in an olive oil:acetone solution (1:3), and thereafter OLE, SPE and OLE + SPE were administered orally for 5 weeks. We determined atopic dermatitis symptoms, serum IgE levels, and levels of cytokine- and gene expression in the dorsal skin and splenocytes, and performed histological and immune cell subtype analyses. The expression of skin barrier-related proteins (filaggrin, sirtuin 1, and claudin 1) was also evaluated.ResultsThe OLE + SPE combination significantly ameliorated atopic dermatitis symptoms, including dermatitis scores, and reduced epidermal thickness and infiltration of different inflammatory cells in mice with DNCB-induced atopic dermatitis. It also significantly reduced the number of CD4⁺, CD8⁺, and CD4⁺/CD69⁺ T cells; immunoglobulin E-producing B cells (CD23⁺/B220⁺) in the axillary lymph nodes; CD3⁺ T-cell eosinophils (chemokine–chemokine receptor 3⁺/CD11b⁺) in the skin; and CD3⁺ T cells, immunoglobulin E-producing B cells (CD23⁺/B220⁺), and eosinophils in peripheral blood mononuclear cells. Additionally, the experimental combination lowered levels of serum immunoglobulin E and histamine, as well as Th2-mediated cytokines, and interleukin-4, -5, and -13, whereas it increased the levels of Th1-mediated cytokine interferon-γ in splenocytes. Furthermore, the preparation significantly restored expression of the skin barrier-related proteins filaggrin, sirtuin 1, and claudin 1, and also reduced the expression of the inflammatory cytokine interleukin-6 and chemokine–chemokine receptor 3, as well as the pruritus-related cytokine interleukin-31 and interleukin-31 receptor, in atopic dermatitis skin lesions.ConclusionTaken together, our findings indicate that administration of a combination of OLE and SPE can alleviate atopic dermatitis symptoms by regulating immune balance and skin barrier function and may be an effective therapeutic option for the treatment of atopic dermatitis.     

WBN/Kob-Ht Rats Spontaneously Develop Dermatitis under Conventional Conditions: Another Possible Model for Atopic Dermatitis.

WBN/Kob-Ht rats (Ht-rats) raised under conventional conditions spontaneously developed dermatitis. In this study, we carried out histopathological analysis to elucidate the pathological features of the dermatitis in Ht-rats. We then tried to detect Staphylococcus species recovered from the skin lesions of Ht-rats. We also measured the serum levels of total IgE, IL-4 and IFN-gamma in these rats. The histopathological data indicated that inflammatory cells had infiltrated the skin lesions. Staphylococcus aureus was recovered from the skin lesions, and the serum levels of total IgE and IL-4 were elevated in Ht-rats with dermatitis. These results suggest that dermatitis in Ht-rats is similar to that in the DS-Nh mice, which has recently been proposed as an animal model for human atopic dermatitis.     

Detection and quantification of specific IgE antibodies against eight Malassezia species in sera of patients with atopic dermatitis by using an enzyme-linked immunosorbent assay

The lipophilic yeast Malassezia, a member of the cutaneous microflora, is an exacerbating factor in atopic dermatitis (AD). Of the 11 currently recognized species, M. globosa and M. restricta are found to frequently colonize the skin of AD patients. In this study, we attempted to quantify specific IgE antibodies against eight Malassezia species, namely, M. dermatitis, M. furfur, M. globosa, M. obtusa, M. pachydermatis, M. slooffiae, M. sympodialis, and M. restricta, in sera from AD patients by using an enzyme-linked immunosorbent assay (ELISA). The specific IgE value against M. restricta was greater than those against other Malassezia species. Competitive ELISA inhibition tests revealed that M. restricta contained species specific as well as shared antigens. Therefore, M. restricta could be considered as a candidate diagnostic antigen for detecting anti-Malassezia IgE in sera from AD patients.     

Evaluation of the levels of specific IgE against Cryptococcus diffluens and Cryptococcus liquefaciens in patients with atopic dermatitis

Cryptococcus diffluens and Cryptococcus liquefaciens, 2 basidiomycetous yeasts, frequently colonize the skin of patients with atopic dermatitis (AD). In this study, we investigated the presence of specific IgE antibodies against C. diffluens and C. liquefaciens in the sera of AD patients by using an enzyme immunoassay . Of the 122 AD serum samples tested, 43 (35.2%) and 50 (41.0%) were positive for specific IgE antibodies against C. diffluens and C. liquefaciens, respectively. The levels of specific IgE against the C. diffluens antigen and that against the C. liquefaciens antigen were strongly correlated (r=0.96). In contrast, no remarkable correlation was observed between the levels of specific IgE against the 2 Cryptococcus species and that of specific IgE against Malassezia restricta. Competitive enzyme-linked immunosorbent assay (ELISA) inhibition tests revealed that C. diffluens and C. liquefaciens shared common antigens. This finding was consistent with the IgE immunoblotting data which demonstrated that several IgE-binding proteins with molecular masses of 77, 54, and 30 kDa were recognized in both C. diffluens and C. liquefaciens antigens . These results suggest that fungal components from C. diffluens and C. liquefaciens may act as allergens and play a role in the pathogenesis of AD.     

IL-13Rα2 has a protective role in a mouse model of cutaneous inflammation

IL-13 is expressed in lesions of atopic dermatitis (AD) and has been associated with increased disease severity. IL-13 has two cognate receptors: IL-13Rα1 and IL-13Rα2. Although IL-13Rα2 expression is known to be induced in response to IL-13 in keratinocytes, its function in AD has never been evaluated. We characterized the loss of skin barrier function and the development of cutaneous inflammation in IL-13Rα2-null versus wild-type BALB/c mice following an epicutaneous allergen-sensitization/challenge model that shares similarities with human AD. Mice lacking IL-13Rα2 had significantly increased transepidermal water loss, cutaneous inflammation, peripheral eosinophilia, and IgG1 and IgE levels compared with wild-type mice. The rate of resolution of the cutaneous inflammation was not significantly altered in the IL-13Rα2-null mice. IL-13 induced expression of IL-13Rα2 in keratinocyte cell lines and primary human keratinocytes. Depletion of IL-13Rα2 in a keratinocyte cell line resulted in increased STAT6 signaling in response to IL-13. In conclusion, IL-13Rα2 serves a protective role in the pathogenesis of allergic inflammation and loss of skin barrier function in a mouse model of AD, suggesting that it may be an important endogenous regulator of IL-13-induced cutaneous inflammation in humans.