Src-type tyrosine kinase p56lck is critical for thymic stromal lymphopoietin-induced allergic rhinitis

Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology
S-Y NamHyun-Ja Jeong

Abstract

Thymic stromal lymphopoietin (TSLP) is a regulator of mast cell-mediated allergic inflammatory reactions, but the manner in which TSLP contributes to allergic rhinitis (AR) remains unclear. Here, we sought to determine that TSLP plays a crucial role in AR by interacting with Src-type tyrosine kinase p56lck and STAT6 and promoting mast cells degranulation. The effects of TSLP on mast cell degranulation and AR were analysed in human mast cell line (HMC-1 cells), ovalbumin (OVA)-induced AR animal model, and human subjects. Small interfering RNA experiments were performed in HMC-1 cells and OVA-induced AR model. Immune responses were analysed by enzyme-linked immunosorbent assay, Western blotting, immunoprecipitation, and histological studies. Thymic stromal lymphopoietin levels and mast cell-derived p56lck activation were elevated in human subjects with AR, and in AR mice, exogenous TSLP accelerated TH2-allergic inflammatory reactions by up-regulating p56lck and STAT6. On the other hand, depletion of TSLP, p56lck, and STAT6 ameliorated clinical symptoms in AR mice. The selective inhibitor of p56lck, damnacanthal, inhibits AR reactions. Collectively, these observations suggest a role for TSLP/p56lck/STAT6 in AR and offer insight in...Continue Reading

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Citations

Dec 14, 2019·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Graham RobertsJudith A Woodfolk
Jun 20, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Na-Ra HanHi-Joon Park
Oct 29, 2021·Immunopharmacology and Immunotoxicology·Jun-Ho YeomHyun-Ja Jeong

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