A thymic stromal lymphopoietin–responsive dendritic cell subset mediates allergic responses in the upper airway mucosa
| Autor: | Einar Gran, Espen S. Baekkevold, Frode L. Jahnsen, Guro Reinholt Melum, Finn-Eirik Johansen, Yong-Jun Liu, Brenda Van Dieren, Lorant Farkas, Cecilie Scheel |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Receptors CCR7 Thymic stromal lymphopoietin Myeloid Adolescent Immunology Inflammation C-C chemokine receptor type 7 Respiratory Mucosa Plasmacytoid dendritic cell Biology Lymphocyte Activation Antigens CD1 Young Adult chemistry.chemical_compound Th2 Cells Thymic Stromal Lymphopoietin Cell Movement medicine Humans Immunology and Allergy Myeloid Cells Receptors Cytokine Cells Cultured Aged Glycoproteins Cell Differentiation hemic and immune systems Dendritic Cells Dendritic cell Allergens Middle Aged Rhinitis Allergic Up-Regulation medicine.anatomical_structure chemistry Polyinosinic:polycytidylic acid STAT protein Cytokines Female medicine.symptom Immunologic Memory |
| Zdroj: | Journal of Allergy and Clinical Immunology. 134:613-621.e7 |
| ISSN: | 0091-6749 |
| DOI: | 10.1016/j.jaci.2014.05.010 |
| Popis: | Background Thymic stromal lymphopoietin (TSLP) controls allergic T H 2 inflammatory responses through induction of distinct activation programs in dendritic cells (DCs). However, knowledge about TSLP receptor expression and functional consequences of receptor activation by DCs residing in the human respiratory tract is limited. Objective We wanted to identify TSLP-responding DC populations in the human upper airway mucosa and assess the TSLP-mediated effects on such DCs in allergic airway responses. Results We found that the TSLP receptor was constitutively and preferentially expressed by myeloid CD1c + DCs in the human airway mucosa and that the density of this DC subset in nasal mucosa increased significantly after in vivo allergen challenge of patients with allergic rhinitis. In vitro , TSLP strongly enhanced the capacity of CD1c + DCs to activate allergen-specific memory CD4 + T cells. Moreover, TSLP rapidly induced CCR7 expression on CD1c + DCs. However, T H 2 cytokines attenuated TSLP-mediated CCR7 induction, thus inhibiting the TSLP-induced DC migration potential to the draining lymph nodes. Conclusion Our results suggest that TSLP-mediated activation of human nasal mucosal CD1c + DCs triggers CCR7-dependent migration to the draining lymph nodes and enhances their capacity to initiate T H 2 responses. However, the observation that T H 2 cytokines abrogate the induction of CCR7 implies that during a T H 2-mediated inflammatory reaction, TLSP-activated CD1c + DCs are retained in the inflamed tissue to further exacerbate local inflammation by activating local antigen-specific memory T H 2 cells. |
| Databáze: | OpenAIRE |
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