Thymic stromal lymphopoietin expression is increased in the horny layer of patients with atopic dermatitis

Sano, Yohei; Masuda, Koji; Tamagawa‐Mineoka, Risa; Matsunaka, Hiroshi; Murakami, Yumi; Yamashita, Ryoko; Morita, Eishin; Katoh, Norito

doi:10.1016/j.jdermsci.2012.11.348

Cited by 32 publications

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“…Serum TSLP of AD patients and mice with barrier disruption (FATP4 mutation) showed significant increase of these parameters compared to healthy controls, but the direct correlation between serum TSLP levels and disease severity is still unclear [32][33][34]. A recent investigation postulated that the stratum corneum TSLP level was increased in AD patients, correlated with disease severity (SCORAD), and the authors also suggested that stratum corneum TSLP level could be used as a biomarker of epidermal barrier status [16]. In our study, the serum and stratum corneum TSLP levels were very similar in STAT3-HIES patients compared to healthy controls, which data may also suggest a well-functioning physicochemical skin barrier in the disease and indicate the absence of AD-like skin Fig.…”

Section: Discussionmentioning

confidence: 99%

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Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome

et al. 2015

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Purpose Hyper-IgE syndrome (HIES) is a severe primary immunodeficiency, characterized by increased serum IgE levels as well as recurrent infections and atopic dermatitis (AD)-like skin lesions. AD is a chronic inflammatory skin disease with immunologic alterations (Th2-Th22 polarization) and characteristic skin barrier dysfunctions. Our aim was to investigate physicochemical skin barrier alterations and allergic sensitization in STAT3-HIES patients in order to explore whether skin barrier dysfunction can play a role in the eczematoid skin lesions in these patients. Methods In our experiments STAT3 and FLG mutation analyses were performed in STAT3-HIES (n=7) and AD (n=49) patients. Laboratory parameters (LDH and Eos counts), immunologic alterations (Th17 cell counts), allergic sensitization (total and specific IgE levels, skin prick tests, and medical history records), skin barrier changes [transepidermal water loss (TEWL), skin pH], serum and stratum corneum thymic stromal lymphopoietin (TSLP) levels were also examined.Results Impaired Th17 cell numbers, but normal physicochemical barrier functions, as well as serum and stratum corneum TSLP levels, were found in STAT3-HIES, while these parameters were significantly altered in AD patients. Allergic sensitization was detected in nearly all AD patients, while no signs of sensitization occurred in STAT3-HIES. Conclusions Our study demonstrated that the skin barrier functions of STAT3-HIES patients are not damaged and they differ significantly from the altered skin barrier functions of AD patients. A well-functioning physicochemical skin barrier may be one of the explanations on the contradiction between the extremely high total IgE levels and the lack of allergic sensitization in these patients. Our study underlines the importance of skin barrier in the development of allergic sensitization.

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Section: Discussionmentioning

confidence: 99%

“…The tape-stripping method and measurement of the stratum corneum TSLP expression level were carried out according to the method described in a previous report by Sano et al [16].…”

Section: Measurement Of the Stratum Corneum Tslp Concentrationmentioning

confidence: 99%

Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome

et al. 2015

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“…Increased expression of TSLP is observed in skin lesions of patients with AD (Soumelis et al, 2002;Sano et al, 2013). Mice overexpressing TSLP in keratinocytes develop AD-like symptoms (Li et al, 2005;Yoo et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

“…TSLP evokes itch and is increased in AD skin lesions (Soumelis et al, 2002;Sano et al, 2013). Injection of TSLP into mice triggers acute itch by directly activating sensory neurons (Wilson et al, 2013).…”

Section: Topical Oxaborole Pde Inhibitors For Inflammatory Diseasesmentioning

confidence: 99%

Treatment of Skin Inflammation with Benzoxaborole Phosphodiesterase Inhibitors: Selectivity, Cellular Activity, and Effect on Cytokines Associated with Skin Inflammation and Skin Architecture Changes

Chen¹,

Virtucio²,

Zemska³

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Psoriasis and atopic dermatitis are skin diseases affecting millions of patients. Here, we characterize benzoxaborole phosphodiesterase (PDE)-4 inhibitors, a new topical class that has demonstrated therapeutic benefit for psoriasis and atopic dermatitis in phase 2 or phase 3 studies.are potent PDE4 inhibitors with similar affinity for PDE4 isoforms and equivalent inhibition on the catalytic domain and the full-length enzyme. These benzoxaboroles are less active on other PDE isozymes. Compd4 binds to the catalytic domain of PDE4B2 with the oxaborole group chelating the catalytic bimetal and overlapping with the phosphate in cAMP during substrate hydrolysis, and the interaction extends into the adenine pocket. In cell culture, benzoxaborole PDE4 inhibitors suppress the release of tumor necrosis factor-a, interleukin (IL)-23, IL-17, interferon-g, IL-4, IL-5, IL-13, and IL-22, and these cytokines contribute to the pathologic changes in skin structure and barrier functions as well as immune dysregulation in atopic dermatitis and psoriasis. Treatment with compd3 or N 6 ,29-O-dibutyryladenosine 39,59-cyclic monophosphate increases cAMP response element binding protein phosphorylation in human monocytes and decreases extracellular signal-regulated kinase phosphorylation in human T cells; these changes lead to reduced cytokine production and are among the mechanisms by which compd3 blocks cytokine release. Topical compd3 penetrates the skin and suppresses phorbol myristate acetate-induced IL-13, IL-22, IL-17F, and IL-23 transcription and calcipotriol-induced thymic stromal lymphopoietin expression in mouse skin. Skin thinning is a major dose-limiting side effect of glucocorticoids. By contrast, repeated application of compd3 did not thin mouse skin. These findings show the potential benefits and safety of benzoxaborole PDE4 inhibitors for the treatment of psoriasis and atopic dermatitis.

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“…Skinspecific overexpression of TSLP induces AD-like phenotypes in mice, including a dramatic increase in CD4+ Th2 cells expressing cutaneous homing receptors and elevated serum levels of IgE [11]. TSLP is overexpressed in the skin stratum corneum, and its expression correlates with the severity of the AD index score and epidermal barrier function, such as stratum corneum hydration and transepidermal water loss [12]. In fact, TSLP appears to be a key cytokine for the progression of the atopic march (atopic dermatitis to asthma), and treatment with anti-TSLP compounds is expected to have important clinical effects [13].…”

Section: Discussionmentioning

confidence: 99%

295 Epidermal growth factor relieves inflammatory signals in Staphylococcus aureus treated human epidermal keratinocytes and atopic dermatitis-like skin lesions in Nc/Nga mice

Lee

Choi

Kang

et al. 2017

Journal of Investigative Dermatology

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Atopic dermatitis (AD) is a chronic inflammatory skin disease with a defective immunologic barrier, which is aggravated by Staphylococcus aureus (S. aureus). Epidermal growth factor (EGF) suppresses inflammation and EGF receptor inhibitors increased S. aureus colonization. Thus, we investigated the potential roles of EGF in AD, which is often aggravated by S. aureus. We determined how EGF affects the expression of inflammatory cytokines and antimicrobial peptides (AMPs) in human epidermal keratinocytes (HEKs) treated with heat-inactivated S. aureus (HKSA) in vitro and 2,4-dinitrochlorobenzene-induced AD-like skin lesions in Nc/Nga mice. HKSA increased IL-6 and NF B expression; EGF treatment had the opposite effect. EGF increased human defensin-2 expression in HEKs and murine defensin-3 in mice. In mice, both EGF and pimecrolimus groups showed less erythema with significantly reduced inflammation and decreased expression of thymic stromal lymphopoietin. EGF relieved S. aureus-induced inflammation and AD-like skin lesions in Nc/Nga mice. Therefore, EGF could be a potential topical treatment for AD.

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Thymic stromal lymphopoietin expression is increased in the horny layer of patients with atopic dermatitis

Cited by 32 publications

References 0 publications

Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome

Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome

Treatment of Skin Inflammation with Benzoxaborole Phosphodiesterase Inhibitors: Selectivity, Cellular Activity, and Effect on Cytokines Associated with Skin Inflammation and Skin Architecture Changes

295 Epidermal growth factor relieves inflammatory signals in Staphylococcus aureus treated human epidermal keratinocytes and atopic dermatitis-like skin lesions in Nc/Nga mice

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