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 language | English |
|---|---|
| Pages (from-to) | 520-529 |
| Number of pages | 10 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 43 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 1 2010 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
- Pulmonary and Respiratory Medicine
- Molecular Biology
- Clinical Biochemistry
Cite this
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. / McGee, Halvor S.; Stallworth, Arthur L.; Agrawal, Tanupriya; Shao, Zhifei; Lorence, Lindsey; Agrawal, Devendra K.
In: American Journal of Respiratory Cell and Molecular Biology, Vol. 43, No. 5, 01.11.2010, p. 520-529.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - McGee, Halvor S.
AU - Stallworth, Arthur L.
AU - Agrawal, Tanupriya
AU - Shao, Zhifei
AU - Lorence, Lindsey
AU - Agrawal, Devendra K.
PY - 2010/11/1
Y1 - 2010/11/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=78149343572&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2009-0241OC
DO - 10.1165/rcmb.2009-0241OC
M3 - Article
C2 - 19933379
AN - SCOPUS:78149343572
VL - 43
SP - 520
EP - 529
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 5
ER -