Atopic dermatitis: the skin barrier and beyond

Tsakok, Teresa; Woolf, Richard; Smith, Catherine; Weidinger, Stephan; Flohr, Carsten

doi:10.1111/bjd.16934

Cited by 211 publications

(211 citation statements)

References 132 publications

(151 reference statements)

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“…In addition, from what is known from the general population, the pathogenesis of atopic dermatitis is complicated by contributions from other cytokines . While T H 2 cytokines are associated with the acute phase of allergic inflammation in the skin and contribute to barrier dysfunction, dysregulation of other cytokines including T H 1 cytokines paradoxically contributes to chronic allergic inflammation in the skin.…”

Section: Allergic Diseasementioning

confidence: 99%

Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome

Jing

Angelus

et al. 2018

Immunological Reviews

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Summary: DOCK8 immunodeficiency syndrome (DIDS) is a progressive combined immunodeficiency that can be distinguished from other combined immunodeficiencies or hyperimmunoglobulinemia E syndromes in featuring 1) profound susceptibility to virus infections of the skin, with associated skin cancers, and 2) severe food allergies. The DOCK8 locus has many repetitive sequence elements that predispose to the generation of large germline deletions as well as recombination-mediated somatic DNA repair. Residual DOCK8 protein contributes to the variable disease phenotype. The severe virus infections of the skin, and probably also VZV-associated vasculopathy, reflect an important function of DOCK8, which is normally required to maintain lymphocyte shape integrity as the cells migrate through dense tissues. Loss of DOCK8 also causes immune deficits through other mechanisms including a milder generalized cell survival defect and skewing of T helper cell subsets. Recent work has uncovered roles for DOCK8 in dendritic cell responses that can also help explain the virus susceptibility, as well as in regulatory T cells that might help explain autoimmunity in a minority of patients. Fortunately, hematopoietic stem cell transplantation cures the eczema and infection susceptibility of DIDS, but not necessarily the other disease manifestations including food allergies.

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Section: Allergic Diseasementioning

confidence: 99%

Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome

Jing

Angelus

et al. 2018

Immunological Reviews

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“…Patients with AD generally exhibit increased levels of Th2 type cytokines—IL‐4, IL‐5 and IL‐13—during the acute phase of AD and increased levels of Th1 type cytokine IFN‐γ during the chronic phase . Current understanding of the aetiology of AD is that disruption of the epidermal barrier leads to increased permeability of the epidermis, pathological skin inflammation and percutaneous sensitization to allergens . One of the therapeutic approaches aims to maintain or improve epidermal barrier function to ameliorate AD.…”

Section: Introductionmentioning

confidence: 99%

Oral treatment with Aloe polysaccharide ameliorates ovalbumin‐induced atopic dermatitis by restoring tight junctions in skin

Lkhagva-Yondon

Kim

et al. 2019

Scand J Immunol

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Atopic dermatitis (AD) is a chronic inflammatory skin disease. A hallmark of AD is dry itchy skin that results from defects in the epidermal barrier function. Aloe vera is used widely to promote general health and is administered topically to treat skin conditions such as eczema, burns and wounds. However, effects of A vera on AD were not fully elucidated. In this study, we investigated the oral administration of processed A vera gel (PAG) containing low molecular weight Aloe polysaccharides to treat ovalbumin (OVA)‐induced AD in mice. Oral administration of PAG suppressed total and OVA‐specific IgE production in sera and decreased the epidermal thickness of skin. Numbers of Ki‐67‐positive cells were reduced by PAG treatment. Expression levels of tight junction genes, including those that encode ZO‐1, Claudin‐1 and Claudin‐8, were decreased in AD skin lesions, whereas oral administration of PAG partially restored the expression levels of tight junction genes. In addition, IL‐4 and IL‐17A mRNA transcript levels were reduced in skin lesions after PAG treatment. Taken together, our findings suggest that oral administration of PAG ameliorated AD, normalized tight junction gene expression and suppressed inflammatory cytokines in AD skin.

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“…AD is a chronic and recurrent cutaneous inflammatory disease that begins in the early stage of life. The pathogenesis of AD is usually linked to skin barrier alteration and immune dysregulation . Indeed, changes in the stratum corneum (SC) composition, which is the outermost layer of the skin, can facilitate the penetration of allergens that can then be associated with the development of AD .…”

Section: Pollution and Skin Pathologiesmentioning

confidence: 99%

“…The pathogenesis of AD is usually linked to skin barrier alteration and immune dysregulation . Indeed, changes in the stratum corneum (SC) composition, which is the outermost layer of the skin, can facilitate the penetration of allergens that can then be associated with the development of AD . As opposed to the outside‐in model of AD pathogenesis, the inside‐out theory suggests that Th2 cytokines are able to modulate the expression of proteins present in the SC, thereby disrupting the skin barrier …”

Section: Pollution and Skin Pathologiesmentioning

confidence: 99%

“…14,15 Indeed, changes in the stratum corneum (SC) composition, which is the outermost layer of the skin, can facilitate the penetration of allergens that can then be associated with the development of AD. 15 As opposed to the outside-in model of AD pathogenesis, 16 the inside-out theory suggests that Th2 cytokines are able to modulate the expression of proteins present in the SC, thereby disrupting the skin barrier. 17 Although there is still existing controversy between these two theories, one fact is clear; the perturbation of the skin barrier plays a key role in AD, and this perturbation can be induced by environmental pollutant exposure.…”

Section: Cutaneous Tissues As a Gateway For The Outdoor Pollutantsmentioning

confidence: 99%

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Involvement of 4‐hydroxy‐2‐nonenal in pollution‐induced skin damage

et al. 2019

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The effects of environmental insults on human health are a major global concern. Some of the most noxious pollutants that humans are exposed to include ozone (O3), particulate matter (PM), and cigarette smoke (CS). Since the skin is the first line of defense against environmental insults, it is considered one of the main target organs for the harmful insults of air pollution. Thus, there is solid evidence that skin pathologies such as premature aging, atopic dermatitis (AD), and psoriasis are associated with pollutant exposure; all of these skin conditions are also associated with an altered redox status. Therefore, although the mechanisms of action and concentrations of O3, PM, and CS that we are exposed to differ, exposure to all of these pollutants is associated with the development of similar skin conditions due to the fact that all of these pollutants alter redox homeostasis, increasing reactive oxygen species production and oxidative stress. A main product of oxidative stress, induced by exposure to the aforementioned pollutants, is 4‐hydroxy‐2‐nonenal (HNE), which derives from the oxidation of ω‐6 polyunsaturated fatty acids. HNE is a highly reactive compound that can form adducts with cellular proteins and even DNA; it is also an efficient cell signaling molecule able to regulate mitogen‐activated protein kinase pathways and the activity of redox‐sensitive transcription factors such as Nrf2, AP1, and NFκB. Therefore, increased levels of HNE in the skin, in response to pollutants, likely accelerates skin aging and exacerbates existing skin inflammatory conditions; thus, targeting HNE formation could be an innovative cosmeceutical approach for topical applications.

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Atopic dermatitis: the skin barrier and beyond

Cited by 211 publications

References 132 publications

Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome

Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome

Oral treatment with Aloe polysaccharide ameliorates ovalbumin‐induced atopic dermatitis by restoring tight junctions in skin

Involvement of 4‐hydroxy‐2‐nonenal in pollution‐induced skin damage

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