Human and computational models of atopic dermatitis: A review and perspectives by an expert panel of the International Eczema Council

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:143

Review

Eyerich, Kilian^1,2,3  Brown, Sara J.^4,5  White, Bethany E. Perez^6,7  Tanaka, Reiko J.⁸  Bissonette, Robert⁹  Dhar, Sandipan¹⁰  Bieber, Thomas^11,12  Hijnen, Dirk J.¹³  Guttman-Yassky, Emma¹⁴  Irvine, Alan¹⁵  Thyssen, Jacob P.¹⁶  Vestergaard, Christian¹⁷  Werfel, Thomas¹⁸  Wollenberg, Andreas¹⁹  Paller, Amy S.^6,20,21  Reynolds, Nick J.^22,23 

[1] Tech Univ Munich, Dept Dermatol & Allergy, Munich, Germany

[2] HMGU, Ctr Allergy & Environm ZAUM, Munich, Germany

[3] Tech Univ Munich, Munich, Germany

[4] Univ Dundee, Sch Med, Skin Res Grp, Dundee, Scotland

[5] Ninewells Hosp & Med Sch, Dept Dermatol, Dundee, Scotland

[6] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA

[7] Northwestern Univ, Feinberg Sch Med, Skin Tissue Engn Core, Chicago, IL 60611 USA

[8] Imperial Coll London, Dept Bioengn, London, England

[9] Innovaderm Res, Montreal, PQ, Canada

[10] Inst Child Hlth, Dept Pediat Dermatol, Kolkata, India

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

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

[13] Erasmus Univ Med Ctr Erasmus MC, Dept Dermatol, Rotterdam, Netherlands

[14] Icahn Sch Med Mt Sinai, Med Ctr, New York, NY 10029 USA

[15] Trinity Coll Dublin, Natl Childrens Res Ctr, Our Ladys Childrens Hosp, Paediat Dermatol, Dublin, Ireland

[16] Univ Copenhagen, Herlev & Gentofte Hosp, Natl Allergy Res Ctr, Dept Dermatol & Allergy, Copenhagen, Denmark

[17] Aalborg Univ Hosp, Dept Dermatol, Aalborg, Denmark

[18] Hannover Med Sch, Hannover, Germany

[19] Ludwig Maximilians Univ Munchen, Dept Dermatol & Allergy, Munich, Germany

[20] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA

[21] Northwestern Univ, Skin Dis Res Ctr, Feinberg Sch Med, Chicago, IL 60611 USA

[22] Newcastle Univ, Inst Cellular Med, Dermatol Sci, Newcastle Upon Tyne, Tyne & Wear, England

[23] Newcastle Hosp NHS Fdn Trust, Royal Victoria Infirm, Dept Dermatol, Newcastle Upon Tyne, Tyne & Wear, England

关键词: Atopic dermatitis;    atopic eczema;    endotype;    human models;    machine learning;    mechanistic models;    precision medicine;    tissue culture models;    skin equivalents;    systems biology;   

DOI  :  10.1016/j.jaci.2018.10.033

来源: Elsevier

【 摘 要 】

Atopic dermatitis (AD) is a prevalent disease worldwide and is associated with systemic comorbidities representing a significant burden on patients, their families, and society. Therapeutic options for AD remain limited, in part because of a lack of well-characterized animal models. There has been increasing interest in developing experimental approaches to study the pathogenesis of human AD in vivo, in vitro, and in silico to better define pathophysiologic mechanisms and identify novel therapeutic targets and biomarkers that predict therapeutic response. This review critically appraises a range of models, including genetic mutations relevant to AD, experimental challenge of human skin in vivo, tissue culture models, integration of omics data sets, and development of predictive computational models. Although no one individual model recapitulates the complex AD pathophysiology, our review highlights insights gained into key elements of cutaneous biology, molecular pathways, and therapeutic target identification through each approach. Recent developments in computational analysis, including application of machine learning and a systems approach to data integration and predictive modeling, highlight the applicability of these methods to AD subclassification (endotyping), therapy development, and precision medicine. Such predictive modeling will highlight knowledge gaps, further inform refinement of biological models, and support new experimental and systems approaches to AD.

【 授权许可】

Free