Thymic stromal lymphopoietin regulates eosinophil migration via phosphorylation of l-plastin in atopic dermatitis.
Infiltration of eosinophils in atopic dermatitis (AD), which contains inflammatory molecules and cytokines, recruits more inflammatory cells and causes further skin damage. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that induces the proinflammatory Th2 immune response and plays an important role in allergic disease. In this study, we aimed to identify a novel protein that regulates TSLP in eosinophils to further understand the role of eosinophils in atopic dermatitis. Using a proteomics approach, we identified the TSLP-inducible protein l-plastin and confirmed upregulation of l-plastin and p-l-plastin in TSLP-treated human eosinophilic leukaemic (EoL-1) cells and in eosinophils from AD patients. Migration assays showed that migration of eosinophils increased when cells were treated with TSLP and when cells were treated with TSLP and an additional cytokine such as interleukin (IL)-3, IL-4, IL-5 or IL-13, when compared to migration of untreated eosinophils. We also confirmed a positive correlation between phosphorylation of l-plastin and an increase in migration of TSLP and cytokine-treated eosinophils. In addition, phosphorylation of l-plastin was sensitive to PKCβII inhibition. Our results suggest that TSLP-induced phosphorylation of l-plastin affects eosinophil migration, which may be mediated by the protein kinase C signalling pathway in atopic dermatitis, thus suggesting p-l-plastin as a potential drug target for eosinophil-targeted allergy therapy.
Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Ji Yeon
JY
Noh
Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Jung U
JU
Shin
Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Chang Ook
CO
Park
Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Nara
N
Lee
Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Shan
S
Jin
Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Seo Hyeong
SH
Kim
Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Ji Hye
JH
Kim
Department of Environmental Medical Biology and Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, Korea.
Arim
A
Min
Department of Environmental Medical Biology and Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, Korea.
Myeong Heon
MH
Shin
Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea. kwanglee@yuhs.ac.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. kwanglee@yuhs.ac.
Kwang Hoon
KH
Lee
D016022:Case-Control Studies; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D010766:Phosphorylation; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C026742:plastin; D000094632:Thymic Stromal Lymphopoietin
atopic dermatitis; eosinophil; migration; phospho-l-plastin; thymic stromal lymphopoietin