Cellular and molecular immunologic mechanisms in patients with atopic dermatitis

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:138

Article

Werfel, Thomas¹  Biedermann, Tilo³  Eyerich, Kilian³  Gilles, Stefanie^4,5  Guttman-Yassky, Emma^6,7,8  Hoetzenecker, Wolfram⁹  Knol, Edward^10,11  Simon, Hans-Uwe¹²  Wollenberg, Andreas¹³  Bieber, Thomas^14,2  Lauener, Roger^14,15  Schmid-Grendelmeier, Peter^14,16  Traidl-Hoffmann, Claudia^4,5,14  Akdis, Cezmi A.^14,17 

[1] Hannover Med Sch, Dept Dermatol & Allergy, Div Immunodermatol & Allergy Res, Carl Neuberg Str 1, D-30625 Hannover, Germany

[2] Univ Bonn, Dept Dermatol & Allergy, Bonn, Germany

[3] Tech Univ Munich, Dept Dermatol & Allergy, D-80290 Munich, Germany

[4] Tech Univ Munich, UNIKA T, Inst Environm Med, Augsburg, Germany

[5] Helmholtz Zentrum Munchen, Augsburg, Germany

[6] Rockefeller Univ, Lab Investigat Dermatol, New York, NY 10021 USA

[7] Icahn Sch Med Mt Sinai, Dept Dermatol, New York, NY 10029 USA

[8] Icahn Sch Med Mt Sinai, Lab Inflammatory Skin Dis, New York, NY 10029 USA

[9] Cantonal Hosp St Gallen, Dept Dermatol Allergol, St Gallen, Switzerland

[10] Univ Med Ctr Utrecht, Dept Immunol, Utrecht, Netherlands

[11] Univ Med Ctr Utrecht, Dept Dermatol Allergol, Utrecht, Netherlands

[12] Univ Bern, Inst Pharmacol, CH-3012 Bern, Switzerland

[13] Univ Munich, Dept Dermatol & Allergy, Munich, Germany

[14] Christine Kuhne Ctr Allergy Res & Educ, Davos, Switzerland

[15] Childrens Hosp Eastern Switzerland, St Gallen, Switzerland

[16] Univ Zurich, Allergy Unit, CH-8006 Zurich, Switzerland

[17] Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland

关键词: Atopic dermatitis;    skin barrier;    filaggrin;    T(H)2;    IL-4;    IL-13;    IL-31;    IgE;    innate;    adaptive;    skin;   

DOI  :  10.1016/j.jaci.2016.06.010

来源: Elsevier

【 摘 要 】

Atopic dermatitis (AD) is a complex skin disease frequently associated with other diseases of the atopic diathesis. Recent evidence supports the concept that AD can also recognize other comorbidities, such as chronic inflammatory bowel or cardiovascular diseases. These comorbidities might result from chronic cutaneous inflammation or from a common, yet-to-bedefined immunologic background leading to immune deviations. The activation of immune cells and their migration to the skin play an essential role in the pathogenesis of AD. In patients with AD, an underlying immune deviation might result in higher susceptibility of the skin to environmental factors. There is a high unmet medical need to define immunologic endotypes of AD because it has significant implications on upcoming stratification of the phenotype of AD and the resulting targeted therapies in the development of precision medicine. This review article emphasizes studies on environmental factors affecting AD development and novel biological agents used in the treatment of AD. Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor alpha-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players. These targeted molecules can be expressed on or drive the cellular players infiltrating the skin (eg, T lymphocytes, dendritic cells, or eosinophils). Such approaches can have immunomodulatory and thereby beneficial clinical effects on the overall skin condition, as well as on the underlying immune deviation that might play a role in comorbidities. An effect of these immunologic treatments on pruritus and the disturbed microbiome in patients with AD has other potential consequences for treatment.

【 授权许可】

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