Integrin αE(CD103) is induced but plays no pathogenic role in psoriasiform skin lesions of TGFβ1 transgenic mice

T‐cells expressing α_E(CD103), an integrin induced by TGFβ on T‐cells in vitro, accumulate within epithelia in inflammatory disorders, including psoriasis. However, it is unclear, if and how α_E(CD103) contributes to skin inflammation. Using two complementary approaches, we have investigated α_E(CD103) in psoriasis‐like skin inflammation of mice with transgenic epidermal expression of human TGFβ1: α_E(CD103) was inhibited by function‐blocking antibodies in vivo, and double‐mutants with additional α_E(CD103)‐depletion were generated in two different genetic backgrounds. Epidermal hTGFβ1 expression was associated with prominent expression of α_E(CD103) on infiltrating cells. However, neither treatment with α_E(CD103)‐blocking antibodies nor deficiency of α_E(CD103) in double‐mutant mice altered the psoriasis‐like phenotype. In addition, histopathological and flow cytometric analyses revealed similar pathological skin alterations and lymphocyte subgroups in the different mouse strains. Thus, while α_E(CD103) expression is indeed associated with hTGFβ1 in vivo, it has little, if any, influence on the course of the psoriasis‐like phenotype in K5.hTGFβ1 transgenic mice.     

Histamine suppresses regulatory T cells mediated by TGF‐β in murine chronic allergic contact dermatitis

Regulatory T cells (Tregs) suppress effector T cells and ameliorate contact hypersensitivity (CH); however, the role of Tregs in chronic allergic contact dermatitis (CACD) has not been assessed. Repeated elicitation of CH has been used to produce CACD models in mice. We previously showed that the presence of histamine facilitates the creation of eczematous lesions in this model using histidine decarboxylase (HDC) (?/?) mice. Therefore, the effects of histamine on Tregs in the CACD model were investigated in this study. CACD was developed by repeated epicutaneous application of 2, 4, 6‐trinitro‐1‐chlorobenzene (TNCB) on HDC (+/+) and HDC (?/?) murine skin to assess the effects of histamine in CACD. Histamine aggravated CACD in the murine model and suppressed the number of Tregs in the skin. Histamine also suppressed the level of TGF‐β1 in this model. Recombinant TGF‐β1 or anti‐TGF‐β1 antibody was injected into the dorsal dermis of HDC (+/+) mice daily just before TNCB challenge to determine the effects of histamine‐regulated TGF‐β on the Treg population in CACD. Recombinant TGF‐β1 injection promoted the infiltration of Tregs in the skin and the production of IL‐10; however, anti‐TGF‐β1 antibody injection suppressed the number of Tregs in the skin and the production of IL‐10. Histamine suppresses the number of Tregs in CACD, and this effect is mediated by TGF‐β.     

CD109, a novel TGF‐β antagonist,decreases fibrotic responses in a hypoxic wound model

Excessive extracellular matrix deposition that occurs in many fibrotic skin disorders such as hypertrophic scarring and scleroderma is often associated with hypoxia. CD109 is a novel TGF‐β co‐receptor and TGF‐β antagonist shown to inhibit TGF‐β‐induced extracellular matrix protein production in vitro. We examined whether CD109 is able to regulate extracellular matrix deposition under low oxygen tension in vivo using transgenic mice overexpressing CD109 in the epidermis. By creating dorsal bipedicle skin flaps with centrally located excisional wounds in these mice and their wild‐type littermates, we generated a novel murine hypoxic wound model. Mice were sacrificed on 7 or 14 days post‐wounding, and tissues were harvested for histological and biochemical analysis. Hypoxic wounds in both transgenic and wild‐type mice showed increased levels of HIF‐1α and delayed wound closure, validating this model in mice. Hypoxic wounds in CD109 transgenic mice demonstrated decreased collagen type 1 and fibronectin expression, and reduced dermal thickness on day 7 post‐wounding as compared to those in wild‐type mice and to non‐hypoxic control wounds. These results suggest that CD109 decreases extracellular matrix production and fibrotic responses during hypoxic wound healing. Manipulating CD109 levels may have potential therapeutic value for the treatment of fibrotic skin disorders associated with poor oxygen delivery.     

8-Methoxypsoralen plus UVA treatment increases the proportion of CLA+ CD25+ CD4+ T cells in lymph nodes of K5.hTGFβ1 transgenic mice

Abstract: 8‐Methoxypsoralen plus UVA (PUVA) photochemotherapy is an effective treatment for many skin diseases including psoriasis. However, its exact mechanism of therapeutic action is incompletely understood. Previously, in K5.hTGFβ1 transgenic psoriatic mice, we found that PUVA induces Foxp3+ CD25+ CD4+ regulatory T cells in both lymph node and spleen. Now, in the same model, we investigated whether cutaneous lymphocyte‐associated antigen (CLA) mediates PUVA’s effect on homing of CD25+ CD4+ T cells to the lymph nodes of K5.hTGFβ1 transgenic mice. We found that a low dose of topical PUVA maximally increased the proportion of CLA + CD25+ CD4 + T cells in the lymph nodes by up to 8‐fold. We also observed an increased number of Foxp3+ CD25+ T cells in the skin of the mice after PUVA treatment. Together, these findings suggest that PUVA affects the homing of regulatory T cells.     

IL‐1 signalling determines the fate of skin grafts expressing non‐self protein in keratinocytes

Please cite this paper as: IL‐1 signalling determines the fate of skin grafts expressing non‐self protein in keratinocytes. Experimental Dermatology 2010; 19 : 723–729. Abstract: Although IL‐1 is a known inflammatory cytokine during pathogen infection, the role of IL‐1 in skin graft rejection, particularly where foreign antigen is expressed exclusively in keratinocytes, is less understood. Here, we use a syngeneic skin graft system, where antigens are expressed in epithelial cells via either a keratin 14 or keratin 5 promoter, to explore the role of IL‐1 in graft rejection and induction of epithelial antigen‐specific effector CD8⁺ T‐cell function. Keratin 5 ovalbumin (K5mOVA) transgenic skin grafts destined for rejection demonstrated increased expression of IL‐1β and its receptors compared to K14 HPV16 E7 transgenic grafts that do not reject spontaneously. Rejection of OVA grafts lacking the IL‐1 receptor (IL‐1R1) was delayed and associated with decreased numbers of antigen‐specific CD8 T cells. In contrast, K14E7 grafts survived on immunocompetent, syngeneic recipients with decreased graft levels of IL‐1β and IL‐1R1 and 2. However, in the absence of the IL‐1 receptor antagonist, IL‐1Ra, skin grafts were spontaneously rejected and an E7‐specific CD8 T‐cell response was primed. Thus, expression of the HPV16E7 oncoprotein in epithelial cells prevents IL‐1β‐associated skin graft rejection and induction of antigen‐specific CD8 T‐cell responses. Enhancing IL‐1β signalling, via blocking of the IL‐1 receptor antagonist, may represent an alternative strategy for treatment of HPV16E7‐associated cancers.     

Role of IL‐10 and TGF‐β in melanoma

IL‐10 and TGF‐β are immunosuppressive cytokines expressed in tumors including melanoma and, therefore, deemed major cause for failing antitumor immune responses. Re‐evaluating their role, we compared their expression by quantitative RT‐PCR in melanoma and skin of healthy individuals, tested their induction in dendritic cells and T cells co‐cultured with tumor cells, and their effects on the immune cells. Both cytokines as well as their receptors were expressed in melanoma at significantly lower levels than in healthy skin. Consequently, the expressions of IL‐10‐responsive SOCS‐3 and TGF‐β‐responsive Smad‐7 were low in tumors but high in healthy skin. T cells co‐cultured with tumor cells developed an anergic state without increased IL‐10 or TGF‐β expression. In vitro tumor‐induced immature dendritic cells produced high IL‐10 levels and less efficiently induced T‐cell proliferation. Nonetheless, they could be induced to mature, and blocking IL‐10 did not alter the capacity of the resulting mature dendritic cells to stimulate T cells. Mature dendritic cells co‐cultured with tumor cells produced increased IL‐10 but decreased TGF‐β and more efficiently induced T‐cell proliferation. The lack of correlation of IL‐10 and TGF‐β with immune deficits in situ and in vitro suggests re‐evaluating their roles in cancer.     

Vaccination with photodynamic therapy-treated macrophages induces highly suppressive T-regulatory cells

Background/purpose: The present study explores whether photodynamic therapy (PDT)‐induced apoptosis can increase the number of tolerogenic regulatory T cells (Treg) and limit collateral tissue damage. Methods: BALB/c mice were vaccinated subcutaneously three times with PDT‐induced apoptotic or thaw‐frozen, necrotic non‐infected autologous macrophages (MΦ). Two weeks after the last vaccination, mice were infected intradermally with 10⁶ promastigotes of Leishmania major. Results: Mice that received PDT‐induced apoptotic MΦ had fewer parasites and higher numbers of Treg than mice vaccinated with thaw‐frozen necrotic MΦ or phosphate‐buffered saline (PBS). Interleukin (IL)‐4 and IL‐6 were significantly suppressed, while IL‐10 was increased in mice that received the PDT‐induced apoptotic MΦ. The role of Treg in this process was confirmed through Treg transfer from vaccinated to naïve mice. Mice receiving CD4⁺CD25⁺ cells from mice vaccinated with PDT‐induced apoptotic MΦ showed smaller lesions 3 weeks after infection and lower parasitic burdens than mice that received Tregs from mice of thaw‐frozen necrotic MΦ or PBS groups. These changes were mediated by the depletion of CD3⁺CD8⁺ and NKT cells and increased levels of IL‐12p70 and interferon‐γ, IL‐10, and TGF‐β in the cutaneous leishmaniasis lesions. Conclusion: Vaccination with apoptotic MΦ‐induced tolerogenic Treg cells that limited collateral tissue damage and diminished parasitic burden.     

The HPV16 E6 oncoprotein and UVB irradiation inhibit the tumor suppressor TGFβ pathway in the epidermis of the K14E6 transgenic mouse

High‐risk human papillomaviruses (HR‐HPVs) are the causative agents of cervical cancer, and they are also associated with a subset of head and neck squamous cell carcinomas. In addition, HPVs have also been postulated in the development of non‐melanoma skin cancers (NMSC). In these cancers, the oncogene E6 is best known for its ability to inactivate the tumor suppressor p53 protein. Interestingly, in transgenic mice for HPV16 E6 (K14E6), it was reported that E6 alone induced epithelial hyperplasia and delay in differentiation in skin epidermis independently of p53 inactivation. Transforming growth factor β (TGFβ) is an important regulator of cell growth/differentiation and apoptosis, and this pathway is often lost during tumorigenesis. Ultraviolet radiation B (UVB) exposure activates diverse cellular responses, including DNA damage and apoptosis. In this study, we investigated whether the E6 oncogene alone or in combination with UVB dysregulate some components of the TGFβ pathway in the epidermis of K14E6 mice. We used 8‐day‐old K14E6 and non‐transgenic mice irradiated and unirradiated with a single dose of UVB. We found that the E6 oncogene and UVB irradiation impair the TGFβ pathway in epidermis of K14E6 mice by downregulation of the TGFβ type II receptor (TβRII). This loss of TβRII prevents downstream activation of Smad2 and target genes as p15, an important regulator of cell cycle progression. In summary, the TGFβ signalling in cells of the epidermis is downregulated in our mouse model by both the E6 oncoprotein and the UVB irradiation.     

Increased regulatory T‐cell frequencies in patients with advanced melanoma correlate with a generally impaired T‐cell responsiveness and are restored after dendritic cell‐based vaccination

Please cite this paper as: Increased regulatory T‐cell frequencies in patients with advanced melanoma correlate with a generally impaired T‐cell responsiveness and are restored after dendritic cell‐based vaccination. Experimental Dermatology 2010; 19 : e213–e221. Abstract: Naturally occurring CD4⁺ CD25⁺ regulatory T‐cell (Treg) activity is assumed to facilitate tumor development and progression. To elucidate the possible role of Tregs in the course of melanoma progression, we analysed the frequency of Tregs in the peripheral blood of patients at melanoma stages I–IV and in patients at melanoma stage IV that underwent dendritic cell (DC)‐based immunotherapy. Using CD25, Foxp3, CD127 and HLA‐DR as Treg associated markers, we observed increased Treg frequencies in patients at the late melanoma stage (stage IV) when compared to healthy donors. Accumulation of Tregs in patients with progressed melanoma correlated with a general reduction of T‐cell responsiveness to the recall antigens tetanus toxoid and tuberculin‐GT. However, DC‐based immunotherapy not only restored antigen‐specific immunity, but also decreased the frequency of Tregs in peripheral blood of patients with melanoma. These findings indicate that tumor progression in patients with melanoma result in general immunosuppression that is associated with Treg expansion in the periphery and can be overcome by DC‐based vaccination.     

Foxp3+ regulatory T cells and related cytokines differentially expressed in plaque vs. guttate psoriasis vulgaris

Background Differences in the number of Foxp3+ regulatory T cells (Tregs) in lesional skin and peripheral blood and their functioning in plaque vs. guttate psoriasis have not been reported. Objectives To investigate whether there is a differential expression of Foxp3+ Tregs and a differential regulation of inflammatory cytokines in plaque vs. guttate psoriasis vulgaris. Methods The number and the percentage of Foxp3+ cells in different phases of skin lesions of patients with plaque and guttate psoriasis vulgaris were assessed by immunohistochemical staining. The expression of Foxp3 and interleukin (IL)‐17 protein in CD4 populations was measured by flow cytometry. Inflammatory cytokine production by transforming growth factor‐β1‐induced Foxp3+ Tregs was assessed in an in vitro study. The cytokines in supernatant and serum were determined by enzyme‐linked immunosorbent assay. Results The percentage of Foxp3+ CD3+ cells in the papillary layer was higher than in the reticular layer of dermis and in epidermis (P < 0·05). The numbers of Foxp3+ Tregs in skin lesions and peripheral blood were higher in plaque than in guttate psoriasis, whereas the percentage of IL‐17+ CD4+ cells was higher in guttate than in plaque psoriasis (P < 0·05). The numbers of Foxp3+ cells were positively correlated with the Psoriasis Severity Index score of skin lesions (P < 0·0001), and the percentages of Foxp3+ CD4+ cells in peripheral blood were positively correlated with the Psoriasis Area and Severity Index score of patients (P < 0·05). The inhibitory functions of Tregs to IL‐17 and IL‐6 in guttate psoriasis and to tumour necrosis factor‐α in plaque psoriasis were deficient. Conclusions Differential expression and regulatory functioning for inflammatory cytokine production by Foxp3+ Tregs may imply a different immunopathogenesis for plaque and guttate psoriasis.     

Platelets are important for the development of immune tolerance: Possible involvement of TGF‐β in the mechanism

Platelets have diverse roles in immune processes in addition to their key functions in haemostasis and thrombosis. Some studies imply that platelets may be possibly related to the immune tolerance induction. However, the role of platelets in the development of immune tolerance is not fully understood. The purpose of this study was to investigate the role of platelets in the development of regulatory mechanisms responsible for cutaneous inflammation using a mouse model of low zone tolerance (LZT). Mice were treated with 2,4,6‐trinitro‐1‐chlorobenzene (TNCB) 8 times every other day for tolerance induction with administration of anti‐platelet antibody or control antibody during the tolerance induction phase every 3 days. After the treatment for the tolerance induction, mice were sensitized and then challenged with TNCB. The contact hypersensitivity (CHS) was significantly decreased at 24 hours after challenge in the mice with LZT than in those without LZT. Platelet depletion via administration of anti‐platelet antibody reversed the inhibition of CHS and reduced the frequency of Foxp3⁺ Tregs in the inflamed skin and draining lymph nodes in mice with LZT. In addition, repeated low‐dose skin exposure resulted in elevated plasma levels of transforming growth factor (TGF)‐β1. Interestingly, platelet depletion reduced plasma TGF‐β1 levels of mice with LZT. Furthermore, the CHS response was reduced by administration of recombinant TGF‐β1 during platelet depletion in mice with LZT. Administration of anti‐TGF‐β antibody reversed the inhibition of the CHS responses. These results suggest that platelets are involved in the induction of immune tolerance via the release of TGF‐β1.     

CD4+ T cells producing interleukin (IL)‐17, IL‐22 and interferon‐γ are major effector T cells in nickel allergy

Background It has been suggested that interleukin (IL)‐17 and IL‐22 play important roles in the elicitation of human allergic contact dermatitis; however, the frequencies of T cell subtypes producing IL‐17 and IL‐22 in human allergic contact dermatitis are unknown. Objectives To determine the frequencies of CD4⁺, CD8⁺ and γδ T cells producing IL‐17, IL‐22 and interferon (IFN)‐γ in the blood and skin from nickel‐allergic patients. Patients/materials/methods Blood samples were collected from 14 patients and 17 controls, and analysed by flow cytometry. Biopsies were taken from 5 patients and 6 controls, and analysed by immunohistochemistry and flow cytometry of skin lymphocytes. Results We found an increased frequency of γδ T cells in the blood, but no differences in the distribution of cytokine‐producing CLA⁺ T cell subtypes in nickel‐allergic patients as compared with controls. In nickel‐allergic patients, there was massive cellular infiltration dominated by CD4⁺ T cells producing IL‐17, IL‐22 and IFN‐γ in nickel‐challenged skin but not in vehicle‐challenged skin. Conclusion CD4⁺ T cells producing IL‐17, IL‐22 and IFN‐γ are important effector cells in the eczematous reactions of nickel‐induced allergic contact dermatitis in humans.     

NADPH oxidase‐2 is a key regulator of human dermal fibroblasts: a potential therapeutic strategy for the treatment of skin fibrosis

The proliferation of human skin dermal fibroblasts (HDFs) is a critical step in skin fibrosis, and transforming growth factor‐beta1 (TGF‐β1) exerts pro‐oxidant and fibrogenic effects on HDFs. In addition, the oxidative stress system has been implicated in the pathogenesis of skin disease. However, the role of NADPH oxidase as a mediator of TGF‐β1‐induced effects in HDFs remains unknown. Thus, our aim was to investigate the role of NADPH in human skin dermal fibroblasts. Primary fibroblasts were cultured and pretreated with various stimulants. Real‐time Q‐PCR and Western blotting analyses were used for mRNA and protein detection. In addition, siRNA technology was applied for gene knock‐down analysis. Hydrogen peroxide production and 2′,7′‐dichlorofluorescein diacetate (DCFDA) measurement assay were performed. Here, our findings demonstrated that HDFs express key components of non‐phagocytic NADPH oxidase mRNA. TGF‐β1 induced NOX2 and reactive oxygen species formation via NADPH oxidase activity. In contrast, NOX3 was barely detectable, and other NOXs did not display significant changes. In addition, TGF‐β1 phosphorylated MAPKs and increased activator protein‐1 (AP‐1) in a redox‐sensitive manner, and NOX2 suppression inhibited baseline and TGF‐β1‐mediated stimulation of Smad2 phosphorylation. Moreover, TGF‐β1 stimulated cell proliferation, migration, collagen I and fibronectin expression, and bFGF and PAI‐1 secretion: these effects were attenuated by diphenylene iodonium (DPI), an NADPH oxidase inhibitor, and NOX2 siRNA. Importantly, NOX2 siRNA suppresses collagen production in primary keloid dermal fibroblasts. These findings provide the proof of concept for NADPH oxidase as a potential target for the treatment of skin fibrosis.     

Visualizing CD4 T‐cell migration into inflamed skin and its inhibition by CCR4/CCR10 blockades using in vivo imaging model

Background Chemokines are critical mediators of T‐cell homing into inflamed skin. The complex nature of this multicellular response makes it difficult to analyse mechanisms mediating the early responses in vivo. Objectives To visualize directly T‐cell homing into inflamed skin and its inhibition by blockades using a unique noninvasive confocal microscopy. Materials and methods A mouse model of allergic contact dermatitis was used. T cells from oxazolone‐sensitized and ‐challenged Balb/c mice were first analysed phenotypically in vitro. CD4 T cells were then labelled with a tracker dye and transferred into Balb/c‐SCID mice. The recipient mice were challenged with oxazolone and CD4 T‐cell homing into inflamed skin was visualized. Results T cells with the skin homing receptors CCR4 and CCR10 were increased in the affected skin and draining lymph nodes, and effectively attracted by their specific chemokines CCL17, CCL22 and CCL27 in vitro. Using in vivo imaging, T‐cell migration into the inflamed skin was observed at 2 h after application, peaking at 12 h and continuing for 48 h. Simultaneous systemic administration of neutralizing antibodies against CCR4 ligands (CCL17 and CCL22) and CCR10 ligand (CCL27) led to a significant suppression of T‐cell migration and skin inflammation. Conclusions Our data indicate that these tissue‐selective adhesion molecules and chemokine/receptor pathways act in concert to attract specialized T‐cell populations to mediate cutaneous inflammation. The in vivo imaging technique can be applicable to other models of cutaneous diseases to help with better understanding of the pathogenesis and monitoring the therapeutic effects.     

Regulatory T cells in atopic dermatitis: epidermal dendritic cell clusters may contribute to their local expansion

Background  Regulatory T cells (Tregs) have an essential role in tolerance and immune regulation. However, few and controversial data have been published to date on the role and number of these cells in atopic dermatitis (AD).
Objectives  To investigate the number of CD4+CD25+FOXP3+ Tregs and interleukin 10-producing T regulatory type 1 (Tr1) cells in patients with AD.
Methods  Peripheral blood and skin biopsy samples from atopy patch test (APT)-positive patients with acute- and chronic-phase AD were investigated. Immunohistochemistry was applied to identify CD4+CD25+FOXP3+ Tregs in the skin, while flow cytometry was used to detect CD4+CD25highFOXP3+ Tregs and Tr1 cells in the peripheral blood.
Results  In the peripheral blood samples of patients with AD significantly elevated numbers of Tr1 cells were found. Although neither the absolute number nor the percentage of CD4+CD25highFOXP3+ Tregs showed significant alteration in the peripheral blood of patients, increased numbers of FOXP3+ Tregs were detected in skin biopsy specimens. All of the APT-positive skin samples showed epidermal dendritic cell aggregates, morphologically consistent with so-called Langerhans cell microgranulomas, which also contained intermingled FOXP3+ Tregs.
Conclusions  Tr1 cell numbers were elevated in the peripheral blood and increased numbers of CD4+CD25highFOXP3+ Tregs were detected in the skin of patients with AD. The epidermal dendritic cell clusters in APT-positive lesional skin showed a close connection to the FOXP3+ Tregs.     

Cutaneous EBV‐positive γδ T‐cell lymphoma vs. extranodal NK/T‐cell lymphoma: a case report and literature review

Primary cutaneous γδ T‐cell lymphoma and extranodal natural killer (NK)/T‐cell lymphoma (ENKTL), nasal type are two distinct lymphoma entities in the World Health Organization (WHO) classification. We report the case of an aggressive cutaneous lymphoma of γδ T‐cell origin showing overlapping features of both lymphomas. A 78‐year‐old female presented with confluent erythematous plaques with ulcerations over her right thigh. Microscopically, section of the skin showed a diffuse dermal and subcutaneous lymphocytic infiltration with tumor necrosis and angioinvasion. The medium‐ to large‐sized tumor cells expressed CD3, CD8, cytotoxic molecules and T‐cell receptor (TCR)‐γ but not CD4, CD20, CD30, CD56 or βF1. In situ hybridization for Epstein‐Barr virus‐encoded mRNA (EBER) was diffusely positive. Polymerase chain reaction‐based clonality assay showed a clonal TCR‐γ chain gene rearrangement. The features compatible with γδ T‐cell lymphoma include dermal and subcutaneous involvements, cytotoxic phenotype, expression of TCR‐γ, as well as an aggressive course. On the other hand, the diffuse EBER positivity, angioinvasion, tumor necrosis and cytotoxic phenotype may also fit in the diagnosis of an ENKTL of T‐cell lineage. We review the literature on EBER‐positive γδ T‐cell lymphoma and discuss the diagnostic dilemma using the current WHO classification system.     

Oral administration of Escherichia coli Nissle 1917 prevents allergen-induced dermatitis in mice

Abstract: Background: The prevalence of allergies has been linked to Western life style factors including a decrease of microbial exposure. Probiotics, such as Escherichia coli Nissle 1917 (EcN), have been shown to be beneficial for prevention and treatment of several chronic inflammatory diseases. Objective: The aim of this study was to investigate the impact of oral EcN administration on development and outcome of allergen‐induced dermatitis. Methods: In sensitized BALB/c mice, skin inflammation was induced by topical allergen application. EcN was administered orally in a preventive manner. Severity of dermatitis was analysed by evaluation of skin score, local cellular and cytokine profile. The systemic immune response was assessed by analysis of immunoglobulins and allergen‐dependent cytokine response. Results: Oral EcN administration improved allergen‐induced dermatitis dose‐dependently. In parallel, a reduction of epidermal thickness and infiltrating immune cells together with an enhanced number of forkhead box P3 (Foxp3)⁺ cells and a trend of increased IFNγ, IL‐10 and TGFβ expression was detected in eczematous skin. In allergen‐stimulated splenocytes reduced IL‐4 and IFNγ along with an elevated IL‐10 production and a tendency to an increased TGFβ secretion were observed. Conclusions: Our findings indicate that EcN alters the local allergen‐induced immune response by increase of Foxp3⁺ cells and by favouring an immunoregulatory cytokine pattern. Thus, oral administration of EcN might be an effective strategy in prevention and potentially therapy of allergic inflammatory skin diseases.