Antibody blockade of Dectin-2 suppresses house dust mite-induced Th2 cytokine production in dendritic cell- and monocyte-depleted peripheral blood mononuclear cell co-cultures from asthma patients
Abstract 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 ant...
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| Format: | Article |
| Language: | English |
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BMC
2019-12-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | https://doi.org/10.1186/s12929-019-0598-6 |
| _version_ | 1819275003057668096 |
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| author | Ming-Han Chen Ming-Ting Huang Wen-Kuang Yu Shinn-Shing Lee Jia-Horng Wang Ting-Jen R. Cheng Michael R. Bowman Shie-Liang Hsieh |
| author_facet | Ming-Han Chen Ming-Ting Huang Wen-Kuang Yu Shinn-Shing Lee Jia-Horng Wang Ting-Jen R. Cheng Michael R. Bowman Shie-Liang Hsieh |
| author_sort | Ming-Han Chen |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-23T23:17:24Z |
| format | Article |
| id | doaj.art-c062eb9bc197464890eb2f07a165030d |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-12-23T23:17:24Z |
| publishDate | 2019-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-c062eb9bc197464890eb2f07a165030d2022-12-21T17:26:27ZengBMCJournal of Biomedical Science1423-01272019-12-0126111210.1186/s12929-019-0598-6Antibody blockade of Dectin-2 suppresses house dust mite-induced Th2 cytokine production in dendritic cell- and monocyte-depleted peripheral blood mononuclear cell co-cultures from asthma patientsMing-Han Chen0Ming-Ting Huang1Wen-Kuang Yu2Shinn-Shing Lee3Jia-Horng Wang4Ting-Jen R. Cheng5Michael R. Bowman6Shie-Liang Hsieh7Division of Allergy, Immunology & Rheumatology, Department of Medicine, Taipei Veterans General HospitalGenomics Research Center, Academia SinicaDepartment of Medicine, National Yang-Ming UniversitySection of Allergy, Immunology, and Rheumatology, Department of Medicine, Cheng Hsin Rehabilitation Medical CenterDepartment of Chest Medicine, Taipei Veterans General HospitalGenomics Research Center, Academia SinicaInflammation and Immunology Research Unit, Pfizer IncGenomics Research Center, Academia SinicaAbstract 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.https://doi.org/10.1186/s12929-019-0598-6House dust miteDermatophagoides pteronyssinusDectin-2Asthma |
| spellingShingle | Ming-Han Chen Ming-Ting Huang Wen-Kuang Yu Shinn-Shing Lee Jia-Horng Wang Ting-Jen R. Cheng Michael R. Bowman Shie-Liang Hsieh Antibody blockade of Dectin-2 suppresses house dust mite-induced Th2 cytokine production in dendritic cell- and monocyte-depleted peripheral blood mononuclear cell co-cultures from asthma patients Journal of Biomedical Science House dust mite Dermatophagoides pteronyssinus Dectin-2 Asthma |
| title | Antibody blockade of Dectin-2 suppresses house dust mite-induced Th2 cytokine production in dendritic cell- and monocyte-depleted peripheral blood mononuclear cell co-cultures from asthma patients |
| title_full | Antibody blockade of Dectin-2 suppresses house dust mite-induced Th2 cytokine production in dendritic cell- and monocyte-depleted peripheral blood mononuclear cell co-cultures from asthma patients |
| title_fullStr | Antibody blockade of Dectin-2 suppresses house dust mite-induced Th2 cytokine production in dendritic cell- and monocyte-depleted peripheral blood mononuclear cell co-cultures from asthma patients |
| title_full_unstemmed | Antibody blockade of Dectin-2 suppresses house dust mite-induced Th2 cytokine production in dendritic cell- and monocyte-depleted peripheral blood mononuclear cell co-cultures from asthma patients |
| title_short | Antibody blockade of Dectin-2 suppresses house dust mite-induced Th2 cytokine production in dendritic cell- and monocyte-depleted peripheral blood mononuclear cell co-cultures from asthma patients |
| title_sort | antibody blockade of dectin 2 suppresses house dust mite induced th2 cytokine production in dendritic cell and monocyte depleted peripheral blood mononuclear cell co cultures from asthma patients |
| topic | House dust mite Dermatophagoides pteronyssinus Dectin-2 Asthma |
| url | https://doi.org/10.1186/s12929-019-0598-6 |
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