Journal
CYTOKINE
Volume 61, Issue 2, Pages 546-555Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2012.10.025
Keywords
Thymic stromal lymphopoietin; TSLP; Cytokine receptors; Inhibitory antibody; Asthma bronchiale
Funding
- Deutsche Forschungsgemeinschaft (DFG) [FR 854/5-1, VI 193/6-1]
- Thuringer Aufbaubank (European Regional Development Fund) [FE 9034]
- Ministry of Economy, Work and Tourism of Mecklenburg-Vorpommern [V220-630-08-TFMV-F-050]
- Interdisziplinares Zentrum fur Klinische Forschung (IZKF) of the Jena University Hospital
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Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7)-like cytokine with a pivotal role in development and maintenance of atopic diseases such as allergic asthma and atopic dermatitis. Moreover, recent studies show an involvement of TSLP in the progression of various cancers. TSLP signaling is mediated by the TSLP receptor (TSLPR), a heterodimeric type I cytokine receptor. It consists of the IL-7 receptor alpha chain (IL-7R alpha), which is shared with the IL-7 receptor, and the TSLPR alpha chain as a specific subunit. Blocking signal release by TSLP without affecting IL-7 function is a potentially interesting option for the treatment of atopic diseases or certain tumors. By employing the extracellular domain of human TSLPR alpha chain (hTSLPR alpha(ex)) as an antigen, we generated a set of monoclonal antibodies. Several binders to native and/or denatured receptor protein were identified and characterized by cytometry and Western blot analysis. A screen based on a STAT3-driven reporter gene assay in murine pro-B cells expressing a functional hTSLPR yielded two hybridoma clones with specific antagonistic properties towards hTSLP, but not IL-7. Kinetic studies measuring blockade of hTSLP-dependent STAT phosphorylation in a TSLP-responsive cell line revealed an inhibitory constant in the nanomolar range. (c) 2012 Elsevier Ltd. All rights reserved.
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