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Scientists expose protein responsible for allergic diseases

hixxy

Senior Member
Messages
1,229
Location
Australia
Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma
Received: 25 August 2016
Accepted: 15 February 2017
Published online: 03 April 2017

Abstract

The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) is pivotal to the pathophysiology of widespread allergic diseases mediated by type 2 helper T cell (Th2) responses, including asthma and atopic dermatitis. The emergence of human TSLP as a clinical target against asthma calls for maximally harnessing its therapeutic potential via structural and mechanistic considerations. Here we employ an integrative experimental approach focusing on productive and antagonized TSLP complexes and free cytokine. We reveal how cognate receptor TSLPR allosterically activates TSLP to potentiate the recruitment of the shared interleukin 7 receptor α-chain (IL-7Rα) by leveraging the flexibility, conformational heterogeneity and electrostatics of the cytokine. We further show that the monoclonal antibody Tezepelumab partly exploits these principles to neutralize TSLP activity. Finally, we introduce a fusion protein comprising a tandem of the TSLPR and IL-7Rα extracellular domains, which harnesses the mechanistic intricacies of the TSLP-driven receptor complex to manifest high antagonistic potency.

http://www.nature.com/articles/ncomms14937
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
Thymic stromal lymphopoietin (TSLP)1,2, is an interleukin-2 (IL-2) family cytokine produced in response to pathogenic stimuli by skin keratinocytes and epithelial cells in the lung and gut. It regulates immunity at barrier surfaces by driving the activation of immature dendritic cells (DCs), mast cells, basophils, eosinophils and lymphocytes into a type 2 polarizing phenotype

Very interesting! I have had eczema on my face for 10-15 years, maybe longer. It was so bad at one time it use to bleed. I recently have been making great progress treating SIBO and leaky gut.

The healthier I get and therefore my gut gets, the more my eczema has subsided, to the point now where it's 90% gone! It seems clear to me now, that dysbiosis and a leaky gut were causing my eczema. Thanks for posting this very interesting study.:)