Flt3-L increases CD4+CD25+Foxp3+ICOS + cells in the lungs of cockroach-sensitized and -challenged mice

Halvor S. McGee, Jehad H. Edwan, Devendra K. Agrawal

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We previously reported in an ovalbumin-induced model of allergic asthma that Fms-like tyrosine kinase 3 ligand (Flt3-L) reversed airway hyperresponsiveness (AHR) and airway inflammation, and increased the number of regulatory CD11chighCD8αhighCD11blow dendritic cells in the lung. In this study, we investigated the effect of Flt3-L in a clinically relevant aeroallergen-induced asthma on the phenotypic expression of lung T cells. Balb/c mice were sensitized and challenged with cockroach antigen (CRA), and AHR to methacholine was established. These mice received three intraperitoneal injections of anti-CD25 antibody (PC61; 250μg) and Flt3-L (3μg) daily for 10 days. Cytokines and Ig levels in the serum were measured and differential bronchoalveolar lavage fluid (BALF) cell counts were examined. Flt3-L reversed AHR to methacholine to the control level. Flt3-L significantly decreased levels of BALF IL-5, IFN-γ, eosinophilia and substantially increased IL-10 and the number of CD4+CD25+ Forkhead winged helix transcription factor box P3 (Foxp3+) IL-10 + T cells in the lung. Administration of PC61 antibody blocked the effect of Flt3-L and substantially increased AHR, eosinophilia, and BALF IL-5 and IFN-γ levels, and decreased BALF IL-10 levels and the number of CD4+CD25+Foxp3+IL-10+ T cells. Flt3-L significantly decreased CD62-L, but increased inducible costimulatory molecule and Foxp3 mRNA expression in the CD4+CD25+ T cells isolated from lungs of Flt3-L-treated, CRA-sensitized mice compared to CRA-sensitized mice without Flt3-L treatment and PBS control group. Flt3-L significantly inhibited the effect of CRA sensitization and challenge to increase GATA3 expression in lung CD4+CD25+ T cells. Collectively, these data suggest that the therapeutic effect of Flt3-L is mediated by increased density of naturally occurring CD4+CD25 +Foxp3+IL-10+ICOS+ T-regulatory cells in the lung. Flt3-L couldbe a therapeutic strategy for the management and prevention of allergic asthma.

Original languageEnglish
Pages (from-to)331-340
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume42
Issue number3
DOIs
StatePublished - Mar 1 2010

Fingerprint

Cockroaches
Lung
T-cells
Interleukin-10
Bronchoalveolar Lavage Fluid
T-Lymphocytes
Antigens
Fluids
Asthma
Methacholine Chloride
Interleukin-5
Eosinophilia
flt3 ligand protein
Winged-Helix Transcription Factors
Forkhead Transcription Factors
Antibodies
Level control
Ovalbumin
Therapeutic Uses
Regulatory T-Lymphocytes

All Science Journal Classification (ASJC) codes

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

Cite this

Flt3-L increases CD4+CD25+Foxp3+ICOS + cells in the lungs of cockroach-sensitized and -challenged mice. / McGee, Halvor S.; Edwan, Jehad H.; Agrawal, Devendra K.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 42, No. 3, 01.03.2010, p. 331-340.

Research output: Contribution to journalArticle

@article{15e99a9968174c09b6558cceb98cb269,
title = "Flt3-L increases CD4+CD25+Foxp3+ICOS + cells in the lungs of cockroach-sensitized and -challenged mice",
abstract = "We previously reported in an ovalbumin-induced model of allergic asthma that Fms-like tyrosine kinase 3 ligand (Flt3-L) reversed airway hyperresponsiveness (AHR) and airway inflammation, and increased the number of regulatory CD11chighCD8αhighCD11blow dendritic cells in the lung. In this study, we investigated the effect of Flt3-L in a clinically relevant aeroallergen-induced asthma on the phenotypic expression of lung T cells. Balb/c mice were sensitized and challenged with cockroach antigen (CRA), and AHR to methacholine was established. These mice received three intraperitoneal injections of anti-CD25 antibody (PC61; 250μg) and Flt3-L (3μg) daily for 10 days. Cytokines and Ig levels in the serum were measured and differential bronchoalveolar lavage fluid (BALF) cell counts were examined. Flt3-L reversed AHR to methacholine to the control level. Flt3-L significantly decreased levels of BALF IL-5, IFN-γ, eosinophilia and substantially increased IL-10 and the number of CD4+CD25+ Forkhead winged helix transcription factor box P3 (Foxp3+) IL-10 + T cells in the lung. Administration of PC61 antibody blocked the effect of Flt3-L and substantially increased AHR, eosinophilia, and BALF IL-5 and IFN-γ levels, and decreased BALF IL-10 levels and the number of CD4+CD25+Foxp3+IL-10+ T cells. Flt3-L significantly decreased CD62-L, but increased inducible costimulatory molecule and Foxp3 mRNA expression in the CD4+CD25+ T cells isolated from lungs of Flt3-L-treated, CRA-sensitized mice compared to CRA-sensitized mice without Flt3-L treatment and PBS control group. Flt3-L significantly inhibited the effect of CRA sensitization and challenge to increase GATA3 expression in lung CD4+CD25+ T cells. Collectively, these data suggest that the therapeutic effect of Flt3-L is mediated by increased density of naturally occurring CD4+CD25 +Foxp3+IL-10+ICOS+ T-regulatory cells in the lung. Flt3-L couldbe a therapeutic strategy for the management and prevention of allergic asthma.",
author = "McGee, {Halvor S.} and Edwan, {Jehad H.} and Agrawal, {Devendra K.}",
year = "2010",
month = "3",
day = "1",
doi = "10.1165/rcmb.2008-0397OC",
language = "English",
volume = "42",
pages = "331--340",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "3",

}

TY - JOUR

T1 - Flt3-L increases CD4+CD25+Foxp3+ICOS + cells in the lungs of cockroach-sensitized and -challenged mice

AU - McGee, Halvor S.

AU - Edwan, Jehad H.

AU - Agrawal, Devendra K.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - We previously reported in an ovalbumin-induced model of allergic asthma that Fms-like tyrosine kinase 3 ligand (Flt3-L) reversed airway hyperresponsiveness (AHR) and airway inflammation, and increased the number of regulatory CD11chighCD8αhighCD11blow dendritic cells in the lung. In this study, we investigated the effect of Flt3-L in a clinically relevant aeroallergen-induced asthma on the phenotypic expression of lung T cells. Balb/c mice were sensitized and challenged with cockroach antigen (CRA), and AHR to methacholine was established. These mice received three intraperitoneal injections of anti-CD25 antibody (PC61; 250μg) and Flt3-L (3μg) daily for 10 days. Cytokines and Ig levels in the serum were measured and differential bronchoalveolar lavage fluid (BALF) cell counts were examined. Flt3-L reversed AHR to methacholine to the control level. Flt3-L significantly decreased levels of BALF IL-5, IFN-γ, eosinophilia and substantially increased IL-10 and the number of CD4+CD25+ Forkhead winged helix transcription factor box P3 (Foxp3+) IL-10 + T cells in the lung. Administration of PC61 antibody blocked the effect of Flt3-L and substantially increased AHR, eosinophilia, and BALF IL-5 and IFN-γ levels, and decreased BALF IL-10 levels and the number of CD4+CD25+Foxp3+IL-10+ T cells. Flt3-L significantly decreased CD62-L, but increased inducible costimulatory molecule and Foxp3 mRNA expression in the CD4+CD25+ T cells isolated from lungs of Flt3-L-treated, CRA-sensitized mice compared to CRA-sensitized mice without Flt3-L treatment and PBS control group. Flt3-L significantly inhibited the effect of CRA sensitization and challenge to increase GATA3 expression in lung CD4+CD25+ T cells. Collectively, these data suggest that the therapeutic effect of Flt3-L is mediated by increased density of naturally occurring CD4+CD25 +Foxp3+IL-10+ICOS+ T-regulatory cells in the lung. Flt3-L couldbe a therapeutic strategy for the management and prevention of allergic asthma.

AB - We previously reported in an ovalbumin-induced model of allergic asthma that Fms-like tyrosine kinase 3 ligand (Flt3-L) reversed airway hyperresponsiveness (AHR) and airway inflammation, and increased the number of regulatory CD11chighCD8αhighCD11blow dendritic cells in the lung. In this study, we investigated the effect of Flt3-L in a clinically relevant aeroallergen-induced asthma on the phenotypic expression of lung T cells. Balb/c mice were sensitized and challenged with cockroach antigen (CRA), and AHR to methacholine was established. These mice received three intraperitoneal injections of anti-CD25 antibody (PC61; 250μg) and Flt3-L (3μg) daily for 10 days. Cytokines and Ig levels in the serum were measured and differential bronchoalveolar lavage fluid (BALF) cell counts were examined. Flt3-L reversed AHR to methacholine to the control level. Flt3-L significantly decreased levels of BALF IL-5, IFN-γ, eosinophilia and substantially increased IL-10 and the number of CD4+CD25+ Forkhead winged helix transcription factor box P3 (Foxp3+) IL-10 + T cells in the lung. Administration of PC61 antibody blocked the effect of Flt3-L and substantially increased AHR, eosinophilia, and BALF IL-5 and IFN-γ levels, and decreased BALF IL-10 levels and the number of CD4+CD25+Foxp3+IL-10+ T cells. Flt3-L significantly decreased CD62-L, but increased inducible costimulatory molecule and Foxp3 mRNA expression in the CD4+CD25+ T cells isolated from lungs of Flt3-L-treated, CRA-sensitized mice compared to CRA-sensitized mice without Flt3-L treatment and PBS control group. Flt3-L significantly inhibited the effect of CRA sensitization and challenge to increase GATA3 expression in lung CD4+CD25+ T cells. Collectively, these data suggest that the therapeutic effect of Flt3-L is mediated by increased density of naturally occurring CD4+CD25 +Foxp3+IL-10+ICOS+ T-regulatory cells in the lung. Flt3-L couldbe a therapeutic strategy for the management and prevention of allergic asthma.

UR - http://www.scopus.com/inward/record.url?scp=77249160769&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77249160769&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2008-0397OC

DO - 10.1165/rcmb.2008-0397OC

M3 - Article

VL - 42

SP - 331

EP - 340

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 3

ER -