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

S. Y. Nam, H. Y. Kim, N. R. Han, P. D. Moon, J. S. Cho, H. M. Kim, H. J. Jeong

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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 STAT6 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 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. Conclusion: Collectively, these observations suggest a role for TSLP/p56lck/STAT6 in AR and offer insight into potential therapeutic strategies.

Original languageEnglish
Pages (from-to)875-889
Number of pages15
JournalClinical and Experimental Allergy
Volume48
Issue number7
DOIs
Publication statusPublished - Jul 2018

Keywords

  • STAT6
  • TSLP
  • allergic rhinitis
  • degranulation
  • mast cells
  • p56lck

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