Modifications of the Innate Immune System in Atopic Dermatitis

Maintz, Laura; Novak, Natalija

doi:10.1159/000323963

Cited by 47 publications

(35 citation statements)

References 100 publications

(76 reference statements)

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“…However, atopic eczema is unlikely to explain the association between atopy and gammaproteobacteria in the present study, given the lack of significant association between atopy and self-reported atopic eczema in our study population (χ 2 = 3.16, P = 0.08). Previous studies have found increased abundance of Staphylococcus on the skin of individuals with atopic eczema (25,26). We found the same, with staphylococci accounting for 5.7% of all sequences in individuals with atopic eczema versus 4.4% in healthy individuals, a non-statistically significant difference (F = 1.53, P = 0.22).…”

Section: Discussionsupporting

confidence: 79%

Environmental biodiversity, human microbiota, and allergy are interrelated

Hanski

Hertzen

Fyhrquist

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

886

734

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Rapidly declining biodiversity may be a contributing factor to another global megatrend—the rapidly increasing prevalence of allergies and other chronic inflammatory diseases among urban populations worldwide. According to the “biodiversity hypothesis,” reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity. Analyzing atopic sensitization (i.e., allergic disposition) in a random sample of adolescents living in a heterogeneous region of 100 × 150 km, we show that environmental biodiversity in the surroundings of the study subjects’ homes influenced the composition of the bacterial classes on their skin. Compared with healthy individuals, atopic individuals had lower environmental biodiversity in the surroundings of their homes and significantly lower generic diversity of gammaproteobacteria on their skin. The functional role of the Gram-negative gammaproteobacteria is supported by in vitro measurements of expression of IL-10, a key anti-inflammatory cytokine in immunologic tolerance, in peripheral blood mononuclear cells. In healthy, but not in atopic, individuals, IL-10 expression was positively correlated with the abundance of the gammaproteobacterial genus Acinetobacter on the skin. These results raise fundamental questions about the consequences of biodiversity loss for both allergic conditions and public health in general.

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Section: Discussionsupporting

confidence: 79%

Environmental biodiversity, human microbiota, and allergy are interrelated

Hanski

Hertzen

Fyhrquist

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

886

734

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“…However, the function of LCs remains controversial [12][13][14]. In addition, it is not clear up to now, whether LCs are directly activated by allergens or require signals from other cells, such as keratinocytes [15].Keratinocytes are a component of the physical barrier of the skin by formation of tight junctions and production of proteases and antimicrobial peptides [16]. In addition, keratinocytes can secrete proinflammatory cytokines and chemokines and alarmins, such as and thymic stromal lymphopoietin (TSLP) [18], which regulate the influx of inflammatory cells in infection and AD [19].…”

mentioning

confidence: 99%

Requirement of MyD88 signaling in keratinocytes for Langerhans cell migration and initiation of atopic dermatitis‐like symptoms in mice

et al. 2016

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Atopic dermatitis (AD) is a chronic inflammatory disease controlled by the innate and adaptive immune system. To elucidate the impact of innate immune signaling in AD, we analyzed MyD88-deficient mice in a murine model of AD-like dermatitis by epicutaneous sensitization with ovalbumin (OVA). Global MyD88 deficiency led to reduced epidermal thickening and diminished accumulation of macrophages within the inflamed skin. In addition, we observed impaired emigration of Langerhans cells (LCs) out of the epidermis of MyD88-deficient mice. These findings indicate that MyD88 deficiency affects various skin-resident cell types in the AD model. Moreover, production of IFN-g, IL-17, and CCL17 was reduced in skin draining lymph node cells and OVA-specific immunoglobulin levels were lower in MyD88-deficient mice. We further investigated the role of MyD88 in keratinocytes, as keratinocytes contribute to AD pathology. Exclusive expression of MyD88 in epidermal keratinocytes partially restored LC emigration after AD induction and expression of CCL17 in skin draining lymph nodes (LNs), but did not promote epidermal thickening nor production of IL-17. Altogether, these data demonstrate that MyD88 signaling in keratinocytes is able to restore LC migration in an otherwise MyD88-deficient background, and significantly contributes to the development of AD-like dermatitis.Keywords: Allergology r Dermatitis r Innate immunity r Langerhans cells r MyD88 signaling r Skin inflammation Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAtopic dermatitis (AD) is a chronic, inflammatory skin disease [1,2] characterized by pruritic, scaly, and erythematous skin lesions and is caused by genetic, environmental, and immunologic factors Correspondence: Dr. Heike Weighardt e-mail: Heike.weighardt@uni-bonn.de [3]. Activation of the immune system during AD results in a mixed Th1 and Th2 response, but also Th22 and Th17 subsets contribute to the immune response [4]. In the majority of AD patients the disease is associated with the development of allergen-specific IgE titers, however also a non-IgE-associated form exists [2]. * These authors contributed equally to this work.C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 982Sonja Didovic et al. Eur. J. Immunol. 2016. 46: 981-992 The development of AD involves barrier defects caused by mutations in structural genes such as filaggrin or disturbed protease activity in the epidermis [5,6] and a dysregulation of the immune system of the skin [6,7]. Impaired barrier function is characterized by enhanced transepidermal water loss (TEWL), which may enhance entry of pathogens, allergens, or toxins and thereby facilitate activation of the skin immune system [6,7]. The skin dendritic cell (DC) network comprises epidermal Langerhans cells (LCs) and different subsets of dermal DCs (dDCs) [8,9]. Upon antigen acquisition both LCs and dDCs get activated and migrate to the draining lymph nodes (LNs) to induce an immune re...

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“…AD is associated with skin barrier abnormalities and a Th2 immune response [13]. AD lesions display lower levels of AMPs than psoriatic plaques [35,36], and are often infected with Staphylococcus aureus , which is associated with AD flares and severity [37,38]. Herpes simplex virus (HSV) infections can also exacerbate AD and Candida species often colonizes atopic skin [37].…”

Section: Prrs As Villains In Primary Skin Disordersmentioning

confidence: 99%

Pattern Recognition Receptors in Immune Disorders Affecting the Skin

Koning¹,

Simon²,

Zeeuwen³

et al. 2012

J Innate Immun

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Pattern recognition receptors (PRRs) evolved to protect organisms against pathogens, but excessive signaling can induce immune responses that are harmful to the host. Putative PRR dysfunction is associated with numerous immune disorders that affect the skin, such as systemic lupus erythematosus, cryopyrin-associated periodic syndrome, and primary inflammatory skin diseases including psoriasis and atopic dermatitis. As yet, the evidence is often confined to genetic association studies without additional proof of a causal relationship. However, insight into the role of PRRs in the pathophysiology of some disorders has already resulted in new therapeutic approaches based on immunomodulation of PRRs.

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Modifications of the Innate Immune System in Atopic Dermatitis

Cited by 47 publications

References 100 publications

Environmental biodiversity, human microbiota, and allergy are interrelated

Environmental biodiversity, human microbiota, and allergy are interrelated

Requirement of MyD88 signaling in keratinocytes for Langerhans cell migration and initiation of atopic dermatitis‐like symptoms in mice

Pattern Recognition Receptors in Immune Disorders Affecting the Skin

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