Monoclonal antibodies targeting ST2L Domain 1 or Domain 3 differentially modulate IL-33-induced cytokine release by human mast cell and basophilic cell lines
| Autor: | Robert A. Lamb, Yawei Li, Ramachandra Reddy, Brian Jones, Eilyn R. Lacy, Angela Filer, Jin Lu, Catherine Healy, Changbao Liu, Karen E. Duffy, Ted Petley, Sheng-Jiun Wu, Natalie Fursov |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.drug_class medicine.medical_treatment Immunology Enzyme-Linked Immunosorbent Assay Monoclonal antibody Cell Degranulation Cell Line 03 medical and health sciences Mice 0302 clinical medicine Protein Domains medicine Animals Humans Mast Cells Receptor Molecular Biology Mice Inbred BALB C biology Antibodies Monoclonal Surface Plasmon Resonance Mast cell Flow Cytometry Interleukin-33 Molecular biology Interleukin-1 Receptor-Like 1 Protein Recombinant Proteins Cell biology Basophils Interleukin 33 030104 developmental biology Cytokine medicine.anatomical_structure biology.protein Cytokines Antibody Signal transduction Transcriptome 030215 immunology Binding domain |
| Zdroj: | Molecular immunology. 75 |
| ISSN: | 1872-9142 |
| Popis: | The cell-surface receptor ST2L triggers cytokine release by immune cells upon exposure to its ligand IL-33. To study the effect of ST2L-dependent signaling in different cell types, we generated antagonist antibodies that bind different receptor domains. We sought to characterize their activities in vitro using both transfected cells as well as basophil and mast cell lines that endogenously express the ST2L receptor. We found that antibodies binding Domain 1 versus Domain 3 of ST2L differentially impacted IL-33-induced cytokine release by mast cells but not the basophilic cell line. Analysis of gene expression in each cell type in the presence and absence of the Domain 1 and Domain 3 mAbs revealed distinct signaling pathways triggered in response to IL-33 as well as to each anti-ST2L antibody. We concluded that perturbing the ST2L/IL-33/IL-1RAcP complex using antibodies directed to different domains of ST2L have a cell-type-specific impact on cytokine release, and may indicate the association of additional receptors to the ST2L/IL-33/IL-1RAcP complex in mast cells. |
| Databáze: | OpenAIRE |
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