- 作者: Ming-Han Chen, Ming-Ting Huang, Wen-Kuang Yu, Shinn-Shing Lee, Jia-Horng Wang, Ting-Jen R. Cheng, Michael R. Bowman and Shie-Liang Hsieh
- 作者服務機構: 1. Division of Allergy, Immunology & Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 2. Department of Medicine, National Yang-Ming University, Taipei, Taiwan 3. Genomics Research Center, Academia Sinica, Taipei, Taiwan 4. Department of Medicine, National Yang-Ming University, Taipei, Taiwan 5. Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 6. Section of Allergy, Immunology, and Rheumatology, Department of Medicine, Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan 7. Critical Care, Far Eastern Memorial Hospital, Taipei, Taiwan 8. Inflammation and Immunology Research Unit, Pfizer Inc, Cambridge, MA, USA 9. Present address: Immunology and Inflammation Therapeutic Area, Sanofi, Cambridge, MA, USA 10. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan 11. Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan 12. Institute for Cancer Biology and Drug Discovery, Taipei Medical University, 128 Academia Road, Section 2, Nankang, Taipei, 115, Taiwan
- 中文摘要:
- 英文摘要:
Background
Dectin-2, which is a C-type lectin, interacts with the house dust mite (HDM) Dermatophagoides pteronyssinus allergen. This study aimed to investigate whether Dectin-2 blockade by antagonistic monoclonal antibodies (MoAbs) attenuates HDM-induced allergic responses.
Methods
Two anti-Dectin-2 MoAbs were generated and validated for specific binding to Dectin-2 Fc fusion protein (Dectin-2.Fc) and inhibition of Dectin-2.Fc/HDM interaction. Patients with asthma exhibiting high titers of anti-D. pteronyssinus IgE were enrolled. Peripheral blood mononuclear cells with depleted CD14+ monocytes were obtained from these patients and co-cultured with autologous monocyte-derived conventional dendritic cells in the presence of D. pteronyssinus or its group 2 allergens (Der p 2). Interleukin (IL)-5 and IL-13 levels in the culture supernatants were determined using ELISA in the presence or absence of anti-Dectin-2 MoAbs.
Results
Two MoAbs, 6A4G7 and 17A1D10, showed specific binding to recombinant Dectin-2.Fc and inhibited HDM binding to Dectin-2.Fc. Both anti-Dectin-2 MoAbs inhibited IL-5 and IL-13 production in co-cultures with Der p 2 stimulation in a dose-dependent manner. 6A4G7 and 17A1D10 (3 μg/mL) significantly inhibited Der p 2-induced (3 μg/mL) IL-5 production by 69.7 and 86.4% and IL-13 production by 84.0 and 81.4%, respectively. Moreover, this inhibitory effect of the two MoAbs remained significant in the presence of D. pteronyssinus.
Conclusions
Anti-Dectin-2 MoAbs significantly inhibited HDM-induced allergic responses in vitro and therefore have the potential to become therapeutic agents in mite-induced allergic diseases. - 中文關鍵字:
- 英文關鍵字: House dust mite, Dermatophagoides pteronyssinus, Dectin-2, Asthma