TSLP Inhibitors for Asthma: Current Status and Future Prospects

@article{Matera2020TSLPIF,
  title={TSLP Inhibitors for Asthma: Current Status and Future Prospects},
  author={Maria Gabriella Matera and Paola Rogliani and Luigino Calzetta and Mario Cazzola},
  journal={Drugs},
  year={2020},
  volume={80},
  pages={449-458}
}
Thymic stromal lymphopoietin (TSLP) is an allarmin cytokine whose importance in human asthma has been repeatedly documented. Accordingly, targeting of TSLP and TSLP-mediated signalling is considered as an attractive therapeutic strategy to asthma. Tezepelumab, which is the first-in-class anti-TSLP monoclonal antibodies (mAb), is a fully human IgG2λ mAb that binds human TSLP, prevents interaction with its receptor and, consequently, inhibits multiple downstream inflammatory pathways. Because of… 
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An overview of the monoclonal antibody therapeutics market for severe uncontrolled asthma is provided, the underlying pathophysiology that drives TSLP is examined and the use of tezepelumab for the treatment of severe uncontrolled asthmatics is discussed.
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TLDR
A fusion protein comprising a tandem of the TSLPR and IL-7Rα extracellular domains is introduced, which harnesses the mechanistic intricacies ofThe TSLP-driven receptor complex to manifest high antagonistic potency.
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TLDR
Findings are consistent with a key role for TSLP in allergen-induced airway responses and persistent airway inflammation in patients with allergic asthma and whether anti-TSLP therapeutics will have clinical value cannot be determined from these data.
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TLDR
This work provides a proof-of-principle for use of fragments in the inhibition of TSLP:TSLPR complexation and uses unbiased molecular dynamics simulations to develop a Markov state model that characterized the binding pathway of the most interesting compound.
Local blockade of TSLP receptor alleviated allergic disease by regulating airway dendritic cells.
TLDR
It is shown that allergen challenge caused a rapid accumulation of TSLP in the airways of asthmatic mice, correlating well with eosinophils counts and interleukin (IL)-5 productions, and local application of anti-TSLPR prevented Th2-mediated airway inflammation, at least partly, by regulating DCs function.
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TLDR
Macrolides are also effective for reducing asthma exacerbation in patients with severe asthma and hold promise for more effective management of asthma.
TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation
TLDR
It is demonstrated that T SLP promotes systemic basophilia, that disruption of TSLP–TSLPR interactions results in defective basophil responses, and that TSLPR-sufficient basophils can restore TH2-cell-dependent immunity in vivo.
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TLDR
TSLP expression is increased in a subset of patients with severe asthma in spite of high-dose inhaled or oral corticosteroid therapy, and targeting TSLP might only be efficacious in the subset of asthma characterized by increased T SLP expression and T(H)2 inflammation.
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TLDR
The aim of this study was to examine whether TSLP may be involved in the pathogenesis of a proto-typical fibrotic disease, idiopathic pulmonary fibrosis (IPF), and to report for the first time, to the knowledge, that T SLP and its receptor (TSLPR) are highly upregulated in IPF.
A soluble thymic stromal lymphopoietin (TSLP) antagonist, TSLPR‐immunoglobulin, reduces the severity of allergic disease by regulating pulmonary dendritic cells
TLDR
The data suggest that local use of TSLPR‐Ig prevents airway inflammation, at least in part, by regulating DC function, and that blocking TSLP signalling using TSL PR‐IG may be a novel strategy for the treatment of asthma bronchiale.
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