Low-density lipoprotein receptor-related protein 1 attenuates house dust mite-induced eosinophilic airway inflammation by suppressing dendritic cell-mediated adaptive immune responses
| Autor: | Zu-Xi Yu, Xuan Qu, Ankit Saxena, Kenneth R. Jeffries, Amarjit Mishra, Elizabeth M. Gordon, Stewart J. Levine, Amisha V. Barochia, Pradeep K. Dagur, Maryann Kaler, Rosemarie A. Cuento, Xianglan Yao, J. Philip McCoy, Karen J. Keeran |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Dermatophagoides pteronyssinus Immunology Inflammation Mice Transgenic Plasmacytoid dendritic cell Adaptive Immunity Article Allergic sensitization 03 medical and health sciences 0302 clinical medicine Immune system Eosinophilia medicine Immunology and Allergy Animals Humans Antigens Dermatophagoides Toll-like receptor business.industry FOXP3 Dendritic cell Dendritic Cells Allergens Immunoglobulin E Middle Aged Acquired immune system Asthma 030104 developmental biology Immunoglobulin G lipids (amino acids peptides and proteins) Female medicine.symptom business Bronchoalveolar Lavage Fluid Low Density Lipoprotein Receptor-Related Protein-1 030215 immunology |
| Zdroj: | The Journal of allergy and clinical immunology. 142(4) |
| ISSN: | 1097-6825 |
| Popis: | Background Low-density lipoprotein receptor–related protein 1 (LRP-1) is a scavenger receptor that regulates adaptive immunity and inflammation. LRP-1 is not known to modulate the pathogenesis of allergic asthma. Objective We sought to assess whether LRP-1 expression by dendritic cells (DCs) modulates adaptive immune responses in patients with house dust mite (HDM)–induced airways disease. Methods LRP-1 expression on peripheral blood DCs was quantified by using flow cytometry. The role of LRP-1 in modulating HDM-induced airways disease was assessed in mice with deletion of LRP-1 in CD11c + cells ( Lrp1 fl/fl ; CD11c -Cre) and by adoptive transfer of HDM-pulsed CD11b + DCs from Lrp1 fl/fl ; CD11c -Cre mice to wild-type (WT) mice. Results Human peripheral blood myeloid DC subsets from patients with eosinophilic asthma have lower LRP-1 expression than cells from healthy nonasthmatic subjects. Similarly, LRP-1 expression by CD11b + lung DCs was significantly reduced in HDM-challenged WT mice. HDM-challenged Lrp1 fl/fl ; CD11c-Cre mice have a phenotype of increased eosinophilic airway inflammation, allergic sensitization, T H 2 cytokine production, and mucous cell metaplasia. The adoptive transfer of HDM-pulsed LRP-1–deficient CD11b + DCs into WT mice generated a similar phenotype of enhanced eosinophilic inflammation and allergic sensitization. Furthermore, CD11b + DCs in the lungs of Lrp1 fl/fl ; CD11c -Cre mice have an increased ability to take up HDM antigen, whereas bone marrow–derived DCs display enhanced antigen presentation capabilities. Conclusion This identifies a novel role for LRP-1 as a negative regulator of DC-mediated adaptive immune responses in the setting of HDM-induced eosinophilic airway inflammation. Furthermore, the reduced LRP-1 expression by circulating myeloid DCs in patients with eosinophilic asthma suggests a possible role for LRP-1 in modulating type 2–high asthma. |
| Databáze: | OpenAIRE |
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