Epicutaneous sensitization to house dust mite allergen requires IRF4-dependent dermal dendritic cells

Publication date: Available online 9 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Julie Deckers, Dorine Sichien, Maud Plantinga, Justine Van Moorleghem, Manon Vanheerswynghels, Esther Hoste, Bernard Malissen, David Dombrowicz, Martin Guilliams, Karolien De Bosscher, Bart N. Lambrecht, Hamida Hammad
BackgroundExposure to allergens like house dust mite (HDM) via the skin often precedes allergic inflammation in the lung. It was proposed that Th2 sensitization via the skin occurs when skin barrier function is disrupted for example by genetic predisposition, mechanical damage or enzymatic activity of allergens.ObjectiveTo study how HDM applied to unmanipulated skin leads to Th2 sensitization and to study which antigen presenting cells mediate this processMethodsHDM was applied epicutaneously by painting HDM on unmanipulated ear skin, or under an occlusive tape. HDM challenge was via the nose. Mouse strains lacking different dendritic cell (DC) populations were used, and 1-DER T cells carrying a transgenic TCR reactive to Der p 1 allergen used as readout for antigen presentation. The Th2-inducing capacity of sorted skin-derived DC subsets was determined by adoptive transfer to naïve mice.ResultsEpicutaneous HDM application led to Th2 sensitization and eosinophilic airway inflammation upon intranasal HDM challenge. Skin sensitization did not require prior skin damage or enzymatic activity within HDM extract, yet was facilitated by applying the allergen under an occlusive tape. Primary proliferation of 1-DER T cells occurred only in the regional skin draining lymph nodes. Epicutaneous sensitization was found to be driven by two variants of IRF4-dependent dermal conventional dendritic cell (cDC2) subsets, and not by epidermal Langerhans cells.ConclusionThese findings identify skin cDC2 as crucial players in Th2 sensitization to common inhaled allergens that enter the body through the skin, and can provoke features of allergic asthma.

Teaser

Our findings identify skin IRF4-dependent cDC2 and not Langerhans cells as crucial players in Th2 sensitization to HDM. How alterations in skin-expressed proteins or cytokines in patients at risk for developing asthma could interfere with this basic mechanism of DC-driven type 2 immunity will need to be addressed.


http://ift.tt/2kz9Om8