Context-dependent function of TSLP and IL-1β in skin allergic sensitization and atopic march
Justine Segaud, Wenjin Yao, Pierre Marschall, François Daubeuf, Christine Lehalle, Beatriz Germán, P. Meyer, Pierre Hener, Cécile Hugel, Eric Flatter, Marine Guivarch, Laetitia Clauss, Stefan F. Martin, Mustapha Oulad‐Abdelghani, Mei Li
Abstract
Atopic diseases, including atopic dermatitis (AD) and asthma, affect a large proportion of the population, with increasing prevalence worldwide. AD often precedes the development of asthma, known as the atopic march. Allergen sensitization developed through the barrier-defective skin of AD has been recognized to be a critical step leading to asthma, in which thymic stromal lymphopoietin (TSLP) was previously shown to be critical. In this study, using a laser-assistant microporation system to disrupt targeted skin layers for generating micropores at a precise anatomic depth of mouse skin, we model allergen exposure superficially or deeply in the skin, leading to epicutaneous sensitization or dermacutaneous sensitization that is associated with a different cytokine microenvironment. Our work shows a differential requirement for TSLP in these two contexts, and identifies an important function for IL-1β, which is independent of TSLP, in promoting allergen sensitization and subsequent allergic asthma.