Monoclonal antibodies targeting ST2L Domain 1 or Domain 3 differentially modulate IL-33-induced cytokine release by human mast cell and basophilic cell lines.
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.
Biologics Research, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Natalie
N
Fursov
Biologics Research, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Jin
J
Lu
Immunology Discovery, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Catherine
C
Healy
Biologics Research, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Sheng-Jiun
SJ
Wu
Biologics Research, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Eilyn
E
Lacy
Immunology Discovery, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Angela
A
Filer
Immunology Discovery, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Yawei
Y
Li
Immunology Discovery, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Changbao
C
Liu
Immunology Discovery, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Roberta
R
Lamb
Immunology Discovery, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Brian
B
Jones
Biologics Research, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Ramachandra
R
Reddy
Biologics Research, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Ted
T
Petley
Immunology Discovery, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA. Electronic address: kduffy@its.jnj.com.
Karen
K
Duffy
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001491:Basophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000037:antagonists & inhibitors* / Q000276:immunology; D000067596:Interleukin-33 / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D000072417:Protein Domains; D011994:Recombinant Proteins; D020349:Surface Plasmon Resonance; D059467:Transcriptome
D000911:Antibodies, Monoclonal; D016207:Cytokines; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D011994:Recombinant Proteins
Basophils; IL-33; Mast cells; Monoclonal antibody; ST2L