PNAS：异位性皮炎和哮喘的分子联系

科学家利用小鼠模型发现了一种把异位性皮炎（AD）和哮喘联系起来的蛋白质。患有AD的人常常在后来出现过敏性哮喘，而且尽管这两种病都涉及到异常炎症，两者之间的准确联系尚未得到充分理解。

Zhikun Zhang及其同事发现，通过在皮肤中过度制造被称为胸腺基质淋巴生成素（TSLP）的AD炎症调控因子从而触发小鼠的AD，这导致了这些小鼠比暴露在更少剂量的TSLP下的小鼠在后来更容易出现哮喘样症状。这组科学家用了一种已知可以引发TSLP过度制造及实验室小鼠的耳出现AD的化合物，结果发现这些用TSLP诱导化合物处理的小鼠在接触过敏原后的肺部比对照组小鼠出现了远远更加严重的炎症反应。这种哮喘样反应的加重甚至出现在小鼠的任何AD外部症状被治愈的时候。这组科学家说皮肤细胞制造的TSLP很可能进入了一般循环，并加重了哮喘免疫应答。（生物谷Bioon.com）

生物谷推荐原始出处：

PNAS Published online before print February 2, 2009, doi: 10.1073/pnas.0812668106

Thymic stromal lymphopoietin overproduced by keratinocytes in mouse skin aggravates experimental asthma

Zhikun Zhanga, Pierre Henera, Nelly Frossardb, Shigeaki Katoc, Daniel Metzgera, Mei Lia,1,2 and Pierre Chambona,1,2

aDepartment of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, 67404 Illkirch, France;
bInflammation et Environnement dans l'Asthme, Faculté de Pharmacie, Université Louis Pasteur-Strasbourg I, 67404 Illkirch, France; and
cInstitute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan

Atopic dermatitis (AD) is often the initial step in the “atopic march,” given that more than half of AD patients with moderate to severe AD develop asthma later in life. Both AD and asthma share a similar “atopy” phenotype that includes T helper type 2 inflammation with eosinophilia and hyper-IgE immunoglobulinemia, but the molecular mechanisms underlying the “atopic march” remain elusive. In the present study, we show that induced expression of thymic stromal lymphopoietin (TSLP) in mouse epidermal keratinocytes upon topical application of MC903 (a low calcemic analogue of vitamin D3) not only triggers AD as we previously reported but also aggravates experimental allergic asthma induced by ovalbumin sensitization and challenge. Our study, which provides a mouse model to study human “atopic march,” indicates that keratinocyte-produced TSLP may represent an important factor in the link of atopic dermatitis to asthma.