Julie Deckers1, Dorine Sichien2, Maud Plantinga3, Justine Van Moorleghem4, Manon Vanheerswynghels4, Esther Hoste2, Bernard Malissen5, David Dombrowicz6, Martin Guilliams2, Karolien De Bosscher7, Bart N Lambrecht3, Hamida Hammad8. 1. VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium; Receptor Research Laboratories, Nuclear Receptor Lab, VIB Center for Medical Biotechnology, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium. 2. VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. 3. VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands. 4. VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium. 5. Centre d'Immunologie de Marseille-Luminy, Marseille, France. 6. INSERM U1011, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France. 7. Receptor Research Laboratories, Nuclear Receptor Lab, VIB Center for Medical Biotechnology, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium. 8. VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium. Electronic address: hamida.hammad@ugent.be.
Abstract
BACKGROUND: Exposure to allergens, such as house dust mite (HDM), through the skin often precedes allergic inflammation in the lung. It was proposed that TH2 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 TH2 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 TH2-inducing capacity of sorted skin-derived DC subsets was determined by means of adoptive transfer to naive mice. RESULTS: Epicutaneous 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 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 TH2 sensitization to common inhaled allergens that enter the body through the skin and can provoke features of allergic asthma.
BACKGROUND: Exposure to allergens, such as house dust mite (HDM), through the skin often precedes allergic inflammation in the lung. It was proposed that TH2 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 TH2 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 TH2-inducing capacity of sorted skin-derived DC subsets was determined by means of adoptive transfer to naive mice. RESULTS: Epicutaneous 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 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 TH2 sensitization to common inhaled allergens that enter the body through the skin and can provoke features of allergic asthma.
Authors: Caroline Perner; Cameron H Flayer; Xueping Zhu; Pamela A Aderhold; Zaynah N A Dewan; Tiphaine Voisin; Ryan B Camire; Ohn A Chow; Isaac M Chiu; Caroline L Sokol Journal: Immunity Date: 2020-10-23 Impact factor: 31.745
Authors: Marie Godar; Kim Deswarte; Karl Vergote; Michael Saunders; Hans de Haard; Hamida Hammad; Christophe Blanchetot; Bart N Lambrecht Journal: J Allergy Clin Immunol Date: 2018-06-08 Impact factor: 10.793
Authors: Noor H A Suaini; Gaik Chin Yap; Do Phuong Tung Bui; Evelyn Xiu Ling Loo; Anne Eng Neo Goh; Oon Hoe Teoh; Kok Hian Tan; Keith M Godfrey; Bee Wah Lee; Lynette Pei-Chi Shek; Hugo Van Bever; Yap Seng Chong; Elizabeth Huiwen Tham Journal: Clin Exp Allergy Date: 2021-07-31 Impact factor: 5.018