Fms-like tyrosine kinase 3 ligand decreases T helper type 17 cells and suppressors of cytokine signaling proteins in the lung of house dust mite-sensitized and -challenged mice

Halvor S. McGee, Arthur L. Stallworth, Tanupriya Agrawal, Zhifei Shao, Lindsey Lorence, Devendra K. Agrawal

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

We previously reported that Fms-like tyrosine kinase 3 ligand (Flt3-L) reversed airway hyperresponsiveness (AHR) and airway inflammation, and increased the number of regulatory CD11c highCD8α highCD11b low dendritic cells and CD4 +CD25 +ICOS +Foxp3 +IL-10 + T-regulatory cells in the lung of allergen-sensitized and -challenged mice. In this study, we evaluated the effect of Flt3-L on Th17 cells and expression of suppressors of cytokine signaling (SOCS) proteins in the lungs of house dust mite (HDM)-sensitized and -challenged mice. BALB/c mice were sensitized and challenged with HDM, and AHR to methacholine was established. Mice were treated with Flt3-L (5 mg, intraperitoneal) daily for 10 days. Levels of IL-4, -5, -6, -8, and -13, and transforming growth factor (TGF)-β in the bronchoalveolar lavage fluid (BALF) were examined by ELISA. Flt3-L treatment reversed existing AHR to methacholine and substantially decreased eosinophils, neutrophils, IL-5, -6, -8, and IL-13, and TGF-β levels in the BALF. HDM-sensitized and -challenged mice showed a significant increase in lung CD4 +IL-17 +IL-23R +CD25 - T cells with high expression of retinoic acid-related orphan receptor (ROR)-γt transcripts. However, administration of Flt3-L substantially decreased the number of lung CD4 +IL-17 +IL-23R +CD25 - T cells, with significantly decreased expression of ROR-γt mRNA in these cells. HDM sensitization caused a significant increase in the expression of SOCS-1, -3, and -5 in the lung. Flt3-L treatment abolished the increase in SOCS-1 and SOCS-3 proteins, whereas SOCS-5 expression was significantly reduced. These data suggest that the therapeutic effect of Flt3-L in reversing the hallmarks of allergic asthma in a mouse model is mediated by decreasing IL-6 and TGF-β levels in the BALF, which, in turn, decrease CD4 +IL-17 +IL-23R +ROR-γt +CD25 - T cells and the expression of SOCS-1 and SOCS-3 in the lung of HDM-sensitized and -challenged mice.

Original languageEnglish
Pages (from-to)520-529
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume43
Issue number5
DOIs
StatePublished - Nov 1 2010

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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