Document Detail


TSLP acts on infiltrating effector T cells to drive allergic skin inflammation.
MedLine Citation:
PMID:  18711124     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Thymic stromal lymphopoietin (TSLP) is a cytokine expressed by epithelial cells, including keratinocytes, and is important in allergic inflammation. Allergic skin inflammation elicited by epicutaneous immunization of mice with ovalbumin (OVA), a potential model of atopic dermatitis, was severely impaired in TSLPR(-/-) mice, as evidenced by decreased infiltration of eosinophils and decreased local expression of T helper 2 (Th2) cytokines. However, secretion of Th2 cytokines by splenocytes from epicutaneous sensitized TSLPR(-/-) mice in response to OVA was normal. Skin dendritic cells from TSLPR(-/-) mice were normal in their ability to migrate to draining lymph nodes, express activation markers, and induce proliferation and Th2 cytokine production by naïve T cells. CD4(+) T cells from TSLPR(-/-) mice expressed the skin homing receptor E-selectin ligand normally, and homed to the skin normally, but failed to transfer allergic skin inflammation to WT recipients. TSLP enhanced Th2 cytokine secretion in vitro by targeting TSLPR on antigen specific T cells. Intradermal injection of anti-TSLP blocked the development of allergic skin inflammation after cutaneous antigen challenge of OVA immunized WT mice. These findings suggest that TSLP is essential for antigen driven Th2 cytokine secretion by skin infiltrating effector T cells and could be a therapeutic target in allergic skin inflammation.
Authors:
Rui He; Michiko K Oyoshi; Lilit Garibyan; Lalit Kumar; Steven F Ziegler; Raif S Geha
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-08-18
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  105     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-20     Completed Date:  2008-09-16     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11875-80     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Movement
Cell Proliferation / drug effects
Cells, Cultured
Cytokines / immunology*,  metabolism*
Dendritic Cells / cytology,  immunology
Dermatitis / genetics,  immunology*,  metabolism*,  pathology
Female
Hypersensitivity / genetics,  immunology*,  metabolism*,  pathology
Immunity, Innate / immunology
Immunoglobulins
Lymph Nodes / cytology,  immunology
Mice
Mice, Knockout
Ovalbumin / pharmacology
Receptors, Cytokine / deficiency,  genetics,  metabolism
Spleen / cytology,  drug effects,  immunology,  secretion
T-Lymphocytes / immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
AR-047417/AR/NIAMS NIH HHS; N01AI40030/AI/NIAID NIH HHS; R01 AR056113/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Immunoglobulins; 0/Receptors, Cytokine; 0/Tslpr protein, mouse; 0/thymic stromal lymphopoietin; 9006-59-1/Ovalbumin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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