TSLP expression: analysis with a ZsGreen TSLP reporter mouse

J Immunol. 2015 Feb 1;194(3):1372-80. doi: 10.4049/jimmunol.1400519. Epub 2014 Dec 24.

Abstract

Thymic stromal lymphopoietin (TSLP) is a type I cytokine that plays a central role in induction of allergic inflammatory responses. Its principal targets have been reported to be dendritic cells and/or CD4 T cells; epithelial cells are a principal source. We report in this study the development of a reporter mouse (TSLP-ZsG) in which a ZsGreen (ZsG)-encoding construct has been inserted by recombineering into a bacterial artificial chromosome immediately at the translation initiating ATG of TSLP. The expression of ZsG by mice transgenic for the recombinant BAC appears to be a faithful surrogate for TSLP expression, particularly in keratinocytes and medullary thymic epithelial cells. Limited ZsG and TSLP mRNA was observed in bone marrow-derived mast cells, basophils, and dendritic cells. Using the TSLP-ZsG reporter mouse, we show that TNF-α and IL-4/IL-13 are potent inducers of TSLP expression by keratinocytes and that local activation of Th2 and Th1 cells induces keratinocyte TSLP expression. We suggest that the capacity of TSLP to both induce Th2 differentiation and to be induced by activated Th2 cells raises the possibility that TSLP may be involved in a positive feedback loop to enhance allergic inflammatory conditions.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Basophils / metabolism
  • Cholecalciferol / pharmacology
  • Cytokines / genetics*
  • Cytokines / metabolism
  • Dendritic Cells / metabolism
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression*
  • Gene Order
  • Genes, Reporter
  • Genetic Vectors / genetics
  • Interleukin-13 / pharmacology
  • Interleukin-4 / pharmacology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Lymphocyte Activation / immunology
  • Mast Cells / metabolism
  • Mice
  • Mice, Transgenic
  • Recombinant Fusion Proteins / genetics
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Thymic Stromal Lymphopoietin
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Cytokines
  • Interleukin-13
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
  • Cholecalciferol
  • Interleukin-4
  • Thymic Stromal Lymphopoietin
  • TSLP protein, mouse

Associated data

  • GEO/GSE54343