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J Allergy Clin Immunol. 2009 Apr;123(4):917-924.e2. doi: 10.1016/j.jaci.2009.01.052.

Fms-like tyrosine kinase 3 ligand increases a lung DC subset with regulatory properties in allergic airway inflammation.

Author information

1
Department of Biomedical Sciences, Creighton University of School of Medicine, Omaha, NE 68178, USA.

Abstract

BACKGROUND:

Dendritic cell (DC) subsets display different functional roles in regulating immune responses and lead to various outcomes, including T(H)1 versus T(H)2 or regulatory versus immunologic responses. Administration of Fms-like tyrosine kinase 3 (Flt3) ligand prevents and reverses allergic airway inflammation and airway hyperresponsiveness in a mouse model. However, the underlying mechanisms are unclear.

OBJECTIVE:

We characterized and examined the role of lung DC subsets in the therapeutic effect of Flt3 ligand.

METHODS:

DCs were isolated from the lungs of ovalbumin (OVA)-sensitized and OVA-challenged mice treated with recombinant human Flt3 ligand. Two populations of CD11c+ cells labeled with fluorochrome-conjugated antibodies were sorted. The ability of the purified cells to stimulate T-cell proliferation and cytokine secretion patterns by different DC subsets was examined. Also, DCs were adoptively transferred in mice to examine their effect on pulmonary function.

RESULTS:

Two DC populations, CD11c(high)CD11b(low) and CD11c(low)CD11b(high), were identified in the lungs of naive and OVA-sensitized and OVA-challenged mice with and without treatment with Flt3 ligand. The expression levels of CD8alpha, B220, CD19, F4/80, MHC II, CCR7, CD40, programmed death ligand 1, programmed death ligand 2, CD80, and CD86 were distinctly different between the 2 DC populations, which supports the notion that CD11c(high)CD11b(low) and CD11c(low)CD11b(high) DCs potentially have regulatory and immunogenic properties, respectively. Administration of Flt3 ligand increased the DCs with regulatory potential in the lungs of antigen-sensitized mice, and CD11c(high)CD11b(low) DCs acquired a maximum degree of regulatory capacity after Flt3 ligand treatment.

CONCLUSION:

These data suggest that Flt3 ligand reverses airway hyperresponsiveness by regulating the function of lung DCs in a mouse model of allergic airway inflammation.

PMID:
19348927
PMCID:
PMC2690643
DOI:
10.1016/j.jaci.2009.01.052
[Indexed for MEDLINE]
Free PMC Article

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