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

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Abstract
BACKGROUND: Exposure 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. OBJECTIVE: 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 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. 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 two variants of IRF4-dependent dermal conventional dendritic cell (cDC2) subsets, and not by epidermal Langerhans cells. CONCLUSION: These 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.
Keywords
Epicutaneous sensitization, house dust mite, allergy, airway inflammation, skin dendritic cells, CD4(+) T-CELLS, LANGERHANS CELLS, TYPE-2 IMMUNITY, IN-VIVO, CONTACT HYPERSENSITIVITY, MEDIATED-IMMUNITY, ATOPIC-DERMATITIS, PROTEASE ACTIVITY, INHALED ANTIGEN, TIGHT JUNCTIONS

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Citation

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Chicago
Deckers, Julie, Dorine Sichien, Maud Plantinga, Justine Van Moorleghem, Manon Vanheerswynghels, Esther Hoste, Bernard Malissen, et al. 2017. “Epicutaneous Sensitization to House Dust Mite Allergen Requires Interferon Regulatory Factor 4-dependent Dermal Dendritic Cells.” Journal of Allergy and Clinical Immunology 140 (5): 1364–1377.e2.
APA
Deckers, J., Sichien, D., Plantinga, M., Van Moorleghem, J., Vanheerswynghels, M., Hoste, E., Malissen, B., et al. (2017). Epicutaneous sensitization to house dust mite allergen requires interferon regulatory factor 4-dependent dermal dendritic cells. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 140(5), 1364–1377.e2.
Vancouver
1.
Deckers J, Sichien D, Plantinga M, Van Moorleghem J, Vanheerswynghels M, Hoste E, et al. Epicutaneous sensitization to house dust mite allergen requires interferon regulatory factor 4-dependent dermal dendritic cells. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 2017;140(5):1364–1377.e2.
MLA
Deckers, Julie, Dorine Sichien, Maud Plantinga, et al. “Epicutaneous Sensitization to House Dust Mite Allergen Requires Interferon Regulatory Factor 4-dependent Dermal Dendritic Cells.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 140.5 (2017): 1364–1377.e2. Print.
@article{8511496,
  abstract     = {BACKGROUND: Exposure 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.
OBJECTIVE: 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 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 na{\"i}ve 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 two variants of IRF4-dependent dermal conventional dendritic cell (cDC2) subsets, and not by epidermal Langerhans cells.
CONCLUSION: These 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.},
  author       = {Deckers, Julie and Sichien, Dorine and Plantinga, Maud and Van Moorleghem, Justine and Vanheerswynghels, Manon and Hoste, Esther and Malissen, Bernard and Dombrowicz, David and Guilliams, Martin and De Bosscher, Karolien and Lambrecht, Bart and Hammad, Hamida},
  issn         = {0091-6749},
  journal      = {JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY},
  language     = {eng},
  number       = {5},
  pages        = {1364--1377.e2},
  title        = {Epicutaneous sensitization to house dust mite allergen requires interferon regulatory factor 4-dependent dermal dendritic cells},
  url          = {http://dx.doi.org/10.1016/j.jaci.2016.12.970},
  volume       = {140},
  year         = {2017},
}

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