Epicutaneous sensitization to house dust mite allergen requires interferon regulatory factor 4–dependent dermal dendritic cells

• Published in: Journal of allergy and clinical immunology Vol. 140; no. 5; pp. 1364 - 1377.e2
• Main Authors: Deckers, Julie, MSc, Sichien, Dorine, MSc, Plantinga, Maud, PhD, Van Moorleghem, Justine, BSc, Vanheerswynghels, Manon, BSc, Hoste, Esther, PhD, Malissen, Bernard, PhD, Dombrowicz, David, PhD, Guilliams, Martin, PhD, De Bosscher, Karolien, PhD, Lambrecht, Bart N., MD, PhD, Hammad, Hamida, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2017; Elsevier Limited; Elsevier
• Subjects: Adoptive transfer; airway inflammation; Allergens; Allergies; allergy; Allergy and Immunology; Animals; Antigen Presentation; Antigen-presenting cells; Antigens, Dermatophagoides - immunology; Arthropod Proteins - immunology; Asthma; Cell proliferation; Cells, Cultured; Cysteine Endopeptidases - immunology; Dendritic cells; Dendritic Cells - immunology; Der p 1 antigen; Dust; Ear; Enzymatic activity; Epicutaneous sensitization; House dust; house dust mite; Hypersensitivity; Hypersensitivity - immunology; Immune system; Immunology; Inflammation; Interferon; Interferon regulatory factor; Interferon regulatory factor 4; Interferon Regulatory Factors - metabolism; Kinases; Langerhans cells; Langerhans Cells - immunology; Leukocytes (eosinophilic); Life Sciences; Lungs; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mites; Nose; Pattern recognition; Pyroglyphidae - immunology; Receptors, Antigen, T-Cell - genetics; Respiratory tract; Respiratory tract diseases; Skin; Skin - immunology; skin dendritic cells; T cell receptors; Th2 Cells - immunology; Transgenic animals; airway inflammation; LN; TCR; DTR; DN; X-C motif chemokine receptor 1; Diphtheria toxin receptor; MLN; HDM; T-cell receptor; SNP; skin dendritic cells; Bronchoalveolar lavage; MC; Follicular helper T; Mediastinal lymph node; WT; Superficial cervical lymph node; Monocyte-derived cell; Dendritic cell; TEWL; cDC; XCR1; Epicutaneous sensitization; house dust mite; Lymph node; Conventional dendritic cell; T FH; allergy; CFSE; Transepidermal water loss; BAL; Wild-type; Carboxyfluorescein succinimidyl ester; Langerhans cell; SCLN; LC; Double negative; Single nucleotide polymorphism; IRF; Interferon regulatory factor; DC; TFH
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2016.12.970

Background Exposure to allergens, such as house dust mite (HDM), through the skin often precedes allergic inflammation in the lung. It was proposed that TH 2 sensitization through the skin occurs when skin barrier function is disrupted by, for example, genetic predisposition, mechanical damage, or the enzymatic activity of allergens. Objective We sought to study how HDM applied to unmanipulated skin leads to TH 2 sensitization and to study which antigen-presenting cells mediate this process. Methods HDM was applied epicutaneously by painting HDM on unmanipulated ear skin or under an occlusive tape. HDM challenge was through the nose. Mouse strains lacking different dendritic cell (DC) populations were used, and 1-DER T cells carrying a transgenic T-cell receptor reactive to Der p 1 allergen were used as a readout for antigen presentation. The TH 2-inducing capacity of sorted skin-derived DC subsets was determined by means of adoptive transfer to naive mice. Results Epicutaneous HDM application led to TH 2 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 2 variants of interferon regulatory factor 4–dependent dermal type 2 conventional DC subsets and not by epidermal Langerhans cells. Conclusion These findings identify skin type 2 conventional DCs as crucial players in TH 2 sensitization to common inhaled allergens that enter the body through the skin and can provoke features of allergic asthma.