Interleukin-9 is required for allergic airway inflammation mediated by the cytokine TSLP

Immunity. 2013 Feb 21;38(2):360-72. doi: 10.1016/j.immuni.2013.01.007. Epub 2013 Jan 31.

Abstract

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine important for the initiation and development of T helper (Th2) cell-mediated allergic inflammation. In this study, we identified a positive association between interleukin-9 (IL-9) and TSLP concentration in the serum of infants with atopic dermatitis. In primary cell cultures, the addition of TSLP led to an increase in IL-9 production from human and mouse Th9 cells, and induced an increase in signal transducer and activator of transcription 5 (STAT5) activation and binding to the Il9 promoter. In vivo, use of an adoptive transfer model demonstrated that TSLP promoted IL-9-dependent, Th9 cell-induced allergic inflammation by acting directly on T cells. Moreover, transgenic expression of TSLP in the lung stimulated IL-9 production in vivo, and anti-IL-9 treatment attenuated TSLP-induced airway inflammation. Together, our results demonstrate that TSLP promotes Th9 cell differentiation and function and define a requirement for IL-9 in TSLP-induced allergic inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Neutralizing / pharmacology
  • Cell Differentiation / drug effects
  • Cytokines / genetics
  • Cytokines / immunology*
  • Cytokines / pharmacology
  • Dermatitis, Atopic / genetics
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / pathology
  • Gene Expression / drug effects
  • Humans
  • Infant
  • Inflammation / genetics
  • Inflammation / immunology*
  • Inflammation / pathology
  • Interleukin-9 / antagonists & inhibitors
  • Interleukin-9 / genetics
  • Interleukin-9 / immunology*
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Primary Cell Culture
  • Promoter Regions, Genetic
  • Protein Binding
  • Respiratory System / drug effects
  • Respiratory System / immunology
  • Respiratory System / pathology
  • STAT5 Transcription Factor / agonists
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / immunology*
  • Signal Transduction / drug effects
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Th2 Cells / pathology

Substances

  • Antibodies, Neutralizing
  • Cytokines
  • IL9 protein, human
  • Interleukin-9
  • STAT5 Transcription Factor
  • thymic stromal lymphopoietin