Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities

Abstract

Background Atopic dermatitis (AD) is a common inflammatory skin disease with a Th2 and “T22” immune polarity. Despite recent data showing a genetic predisposition to epidermal barrier defects in some patients, a fundamental debate still exists regarding the role of barrier abnormalities versus immune responses in initiating the disease. In order to explore whether there is an intrinsic predisposition to barrier abnormalities and/or background immune activation in AD patients an extensive study of non-lesional AD (ANL) skin is necessary. Objective To characterize ANL skin by determining whether epidermal differentiation and immune abnormalities that characterize lesional AD (AL) are also reflected in ANL skin. Methods We performed genomic and histologic profiling of both ANL and AL skin lesions (n=12 each), compared to normal human skin (n=10). Results We found that ANL is clearly distinct from normal skin with respect to terminal differentiation and some immune abnormalities, and it has a cutaneous expansion of T-cells. We also showed that ANL skin has a variable immune phenotype, which is largely determined by disease extent and severity. Whereas broad terminal differentiation abnormalities were largely similar between involved and uninvolved AD skin, perhaps accounting for the “background skin phenotype,” increased expression of immune-related genes was among the most obvious differences between AL and ANL skin, potentially reflecting the “clinical disease phenotype.” Conclusion Our study implies that systemic immune activation may play a role in alteration of the normal epidermal phenotype, as suggested by the high correlation in expression of immune genes in ANL skin with disease severity index.

The role of emollients in pathogenetic therapy of atopic dermatitis in children

“…Так, было продемонстрировано в экспериментальных условиях [10,12] и в клинической практике [15,33], что при атопическом воспалении цито-кины Th2-профиля могут ингибировать гены терминаль-ной дифференцировки липидов кожного барьера (напри-мер, филаггрина). Установлено, что Th1-цитокины (фактор некроза опухоли альфа, интерферон-гамма) индуцируют синтез керамидов кожного барьера, необходимых для правильного функционирования эпидермального барьера, в то время как Th2-цитокины (IL-4), наоборот, ингибируют их выработку [18,32].…”

Current Views on the Pathogenesis and Principles of External Treatment of Atopic Dermatitis in Children

“…На визуально непоражен-ной коже у детей с атопическим дерматитом уже обна-руживаются признаки субклинического воспаления с увеличением числа Т хелперов (Th2 и Th22 и в мень-шей степени Th17) и провоспалительным цитокино-вым окружением [23]. Усиление инфильтрации Т клеток экспрессирует различные кожные молекулы адгезии, такие как кожный лимфоцитарный антиген, хемокины и липидные хемотактические рецепторы, проникающие в различные слои кожи.…”

Deciphering the complexities of atopic dermatitis: Shifting paradigms in treatment approaches

“…It is noteworthy that AD skin lesions are always associated with underlying immune activation (71)(72)(73). In chronic AD, several underlying features are invariably present: 1) increased skin infiltration by T-cells (approx.…”