scholarly journals Filaggrin and atopic march

2019 ◽  
Vol 29 (2) ◽  
pp. 214-227 ◽  
Author(s):  
Ivana Čepelak ◽  
Slavica Dodig ◽  
Ivan Pavić
Keyword(s):  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Protective Function ◽  
Atopic March ◽  
Adult Age ◽  
Inflammatory Conditions ◽  
Immunological Factors ◽  
And Function ◽  
Allergic Contact

There is an increasing number of experimental, genetic and clinical evidence of atopic dermatitis expression as a pre-condition for later development of other atopic diseases such as asthma, food allergy and allergic rhinitis. Atopic dermatitis is a heterogeneous, recurrent childhood disease, also present in the adult age. It is increasingly attributed to systemic features and is characterized by immunological and skin barrier integrity and function dysregulation. To maintain the protective function of the skin barrier, in particular the maintenance of pH, hydration and antimicrobial functions, the filaggrin, among others, plays a significant role. Filaggrin is a multifunctional, histidine-rich, insoluble protein. The lack of filaggrin is associated with various cutaneous (e.g. ichthyosis vulgaris, allergic contact dermatitis) and non-cutaneous (e.g. diabetes, inflammatory conditions of the gastrointestinal tract) diseases and may be a result of genetic, immunological factors combined with environmental factors. In this review we summarised (emphasized) recent findings in understanding the role of filaggrin in atopic dermatitis and other diseases, participants in the atopic march.

scholarly journals Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 321 ◽  
Author(s):  
Fabio Seiti Yamada Yoshikawa ◽  
Josenilson Feitosa de Lima ◽  
Maria Notomi Sato ◽  
Yasmin Álefe Leuzzi Ramos ◽  
Valeria Aoki ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Complex Disease ◽  
Skin Barrier ◽  
Inflammatory Skin Disease ◽  
Innate And Adaptive Immunity ◽  
Concise Review ◽  
Intense Pruritus ◽  
Immunological Factors

Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense pruritus and xerosis. AD pathogenesis is multifactorial, involving genetic, environmental, and immunological factors, including the participation of Staphylococcus aureus. This bacterium colonizes up to 30–100% of AD skin and its virulence factors are responsible for its pathogenicity and antimicrobial survival. This is a concise review of S. aureus superantigen-activated signaling pathways, highlighting their involvement in AD pathogenesis, with an emphasis on skin barrier disruption, innate and adaptive immunity dysfunction, and microbiome alterations. A better understanding of the combined mechanisms of AD pathogenesis may enhance the development of future targeted therapies for this complex disease.

scholarly journals The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

2021 ◽  
Vol 22 (13) ◽  
pp. 7227
Author(s):  
Lai-San Wong ◽  
Yu-Ta Yen ◽  
Chih-Hung Lee
Keyword(s):  
Atopic Dermatitis ◽  
Environmental Factors ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Disease ◽  
Targeted Therapies ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Inflammatory Molecules

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

scholarly journals Congenital Deficiency of Conventional Dendritic Cells Promotes the Development of Atopic Dermatitis-Like Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yotaro Nishikawa ◽  
Tomohiro Fukaya ◽  
Takehito Fukui ◽  
Tomofumi Uto ◽  
Hideaki Takagi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Atopic Dermatitis ◽  
Immune Responses ◽  
Skin Barrier ◽  
Lymphoid Cells ◽  
Congenital Deficiency ◽  
T Cell Immune Responses ◽  
Group 2 ◽  
And Function ◽  
The Impact

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease characterized by impaired epidermal barrier function and dysregulation of Thelper-2 (TH2)-biased immune responses. While the lineage of conventional dendritic cells (cDCs) are implicated to play decisive roles in T-cell immune responses, their requirement for the development of AD remains elusive. Here, we describe the impact of the constitutive loss of cDCs on the progression of AD-like inflammation by using binary transgenic (Tg) mice that constitutively lacked CD11chi cDCs. Unexpectedly, the congenital deficiency of cDCs not only exacerbates the pathogenesis of AD-like inflammation but also elicits immune abnormalities with the increased composition and function of granulocytes and group 2 innate lymphoid cells (ILC2) as well as B cells possibly mediated through the breakdown of the Fms-related tyrosine kinase 3 ligand (Flt3L)-mediated homeostatic feedback loop. Furthermore, the constitutive loss of cDCs accelerates skin colonization of Staphylococcus aureus (S. aureus), that associated with disease flare. Thus, cDCs maintains immune homeostasis to prevent the occurrence of immune abnormalities to maintain the functional skin barrier for mitigating AD flare.

scholarly journals Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis

2020 ◽  
Vol 21 (8) ◽  
pp. 2867 ◽  
Author(s):  
Gabsik Yang ◽  
Jin Kyung Seok ◽  
Han Chang Kang ◽  
Yong-Yeon Cho ◽  
Hye Suk Lee ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Systemic Disease ◽  
Skin Barrier ◽  
Immune Dysregulation ◽  
Food Allergies ◽  
Atopic Diseases ◽  
Barrier Dysfunction ◽  
Underlying Mechanisms ◽  
Chronic Pruritus ◽  
And Function

Atopic dermatitis (AD) is a common and relapsing skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. While AD was previously thought to occur primarily in children, increasing evidence suggests that AD is more common in adults than previously assumed. Accumulating evidence from experimental, genetic, and clinical studies indicates that AD expression is a precondition for the later development of other atopic diseases, such as asthma, food allergies, and allergic rhinitis. Although the exact mechanisms of the disease pathogenesis remain unclear, it is evident that both cutaneous barrier dysfunction and immune dysregulation are critical etiologies of AD pathology. This review explores recent findings on AD and the possible underlying mechanisms involved in its pathogenesis, which is characterized by dysregulation of immunological and skin barrier integrity and function, supporting the idea that AD is a systemic disease. These findings provide further insights for therapeutic developments aiming to repair the skin barrier and decrease inflammation.

New insights into the role of T cells in atopic dermatitis and allergic contact dermatitis

2001 ◽  
Vol 22 (10) ◽  
pp. 530-532 ◽  
Author(s):  
Axel Trautmann ◽  
Mübeccel Akdis ◽  
Eva-B Bröcker ◽  
Kurt Blaser ◽  
Cezmi A Akdis
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
Contact Dermatitis ◽  
Allergic Contact Dermatitis ◽  
Allergic Contact

scholarly journals 676 Minimum role of filaggrin-gene mutations in the skin barrier function of atopic dermatitis

2018 ◽  
Vol 138 (5) ◽  
pp. S115
Author(s):  
M. Ota ◽  
T. Sasaki ◽  
T. Ebihara ◽  
S. Murata ◽  
S. Kaneko ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Barrier Function ◽  
Gene Mutations ◽  
Skin Barrier ◽  
Skin Barrier Function

scholarly journals Epidermal Barrier Dysfunction in Atopic Dermatitis

2021 ◽  
Vol 79 (3) ◽  
pp. 207-216
Author(s):  
Tiago Fernandes Gomes ◽  
Rebeca Calado ◽  
Margarida Gonçalo
Keyword(s):  
Atopic Dermatitis ◽  
Current Knowledge ◽  
Skin Barrier ◽  
Initial Step ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Atopic March ◽  
T Helper 2 ◽  
Barrier Repair

Impaired skin barrier is one of the hallmarks of atopic dermatitis (AD), with abnormalities in the cornified envelope, lipid lamellae, tight junctions and cutaneous microbiome. These findings are also present in nonlesional skin of AD individuals, suggesting that epidermal barrier defects may be the initial step towards the development of AD and eventually other atopic diseases (atopic march). It is currently known that pathophysiology of AD involves an interplay between this dysfunctional skin barrier and a predominantly type 2 skewed innate and adaptive immune responses, which further disrupt the skin barrier through type 2 cytokines. In this setting, there is enhanced penetration of environmental and food allergens through a deficient barrier, leading to an increased susceptibility to sensitization. During the sensitization process, thymic stromal lymphopoietin (TSLP) polarizes skin dendritic cells to a T-helper 2 response, and TSLP seems to be a key cytokine in the sensitization of food allergy, allergic asthma and rhinitis. In this review, the authors describe the current knowledge of the pathophysiology of the epidermal barrier, its disruption in AD and how it may be involved in the development of atopic comorbidities and the role of barrier repair therapy on the prevention of the atopic march progression.  

scholarly journals Characterisation of the immune cells and cytokines involved in a model of atopic dermatitis

2021 ◽  
Author(s):  
◽  
Karmella Naidoo
Keyword(s):  
Atopic Dermatitis ◽  
Wide Spectrum ◽  
Management Strategies ◽  
Substantial Reduction ◽  
Skin Barrier ◽  
Barrier Dysfunction ◽  
Effector Cells ◽  
Treatment And Prevention ◽  
Inflammatory Parameters

<p>Atopic dermatitis (AD) is a highly debilitating disease with significant health impacts worldwide. It is a chronic and relapsing inflammatory skin disease which often poses a life-long burden for the affected individuals. AD has been a difficult disease to treat as it manifests with a wide spectrum of clinical phenotypes and the current clinical management strategies are non-specific. Therefore, it is imperative to identify specific immunological pathways that could be targeted to treat this disease. Previous studies have documented that AD disease progression is precipitated by a combination of skin barrier dysfunction, itch and immune dysregulation that are responsible for AD progression. However, the precise role of effector cells and cytokines have not been fully elucidated. To address this, I established a clinically relevant model of AD, using the vitamin D analogue, MC903. This MC903 model closely resembles the AD phenotype in patients, including inflammatory parameters, barrier dysfunction, itch, and histopathological characteristics, providing a novel platform to evaluate targets for the treatment and prevention of AD. Furthermore, this model exposed the cells and cytokines that are critically associated with disease severity, including eosinophils, mast cells, TSLP, IL-4 and IL-9, but not CD4+ T cells. The instrumental role of these effector cells and cytokines was established by their stepwise depletion or blockade. Indeed, functional eosinophil depletion via the use of inducible eosinophil (iPHIL) mice significantly ameliorated AD pathology, most notably itch. Similar results were obtained after blockade of the IL-4/IL-13 axis by genetic deletion of STAT6. The clinically more relevant use of soluble inhibitors targeting IL-9 and CRTh2 (in a prophylactic and therapeutic setting, respectively), both resulted in a substantial reduction in AD phenotype. In summary, this body of work led to the identification of key disease-initiating and effector cells and molecules that represent attractive targets for the treatment of AD.</p>

scholarly journals Advances in understanding and managing atopic dermatitis

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1296 ◽  
Author(s):  
Michael Barton ◽  
Robert Sidbury
Keyword(s):  
Atopic Dermatitis ◽  
Natural History ◽  
Skin Disease ◽  
Allergic Sensitization ◽  
Therapeutic Targets ◽  
Skin Barrier ◽  
Immune Dysregulation ◽  
Pruritic Skin

Atopic dermatitis is a chronic, pruritic skin disease characterized by an improperly functioning skin barrier and immune dysregulation. We review proposed atopic dermatitis pathomechanisms, emphasizing how these impact current perspectives on natural history, role of allergic sensitization, and future therapeutic targets.

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