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Src‐type tyrosine kinase p56lck is critical for thymic stromal lymphopoietin‐induced allergic rhinitis
Author(s) -
Nam S.Y.,
Kim H.Y.,
Han N.R.,
Moon P.D.,
Cho J.S.,
Kim H.M.,
Jeong H.J.
Publication year - 2018
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13167
Subject(s) - thymic stromal lymphopoietin , degranulation , tyrosine kinase , immunology , allergic inflammation , mast cell , proto oncogene tyrosine protein kinase src , ovalbumin , cytokine , biology , immune system , kinase , signal transduction , allergy , microbiology and biotechnology , receptor , biochemistry
Summary Background 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. Objective Here, we sought to determine that TSLP plays a crucial role in AR by interacting with Src‐type tyrosine kinase p56lck and STAT 6 and promoting mast cells degranulation. Methods 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. Results Thymic stromal lymphopoietin levels and mast cell‐derived p56lck activation were elevated in human subjects with AR , and in AR mice, exogenous TSLP accelerated TH 2‐allergic inflammatory reactions by up‐regulating p56lck and STAT 6. On the other hand, depletion of TSLP , p56lck, and STAT 6 ameliorated clinical symptoms in AR mice. The selective inhibitor of p56lck, damnacanthal, inhibits AR reactions. Conclusion Collectively, these observations suggest a role for TSLP /p56lck/ STAT 6 in AR and offer insight into potential therapeutic strategies.