Abstract
Fms-like tyrosine kinase 3 ligand (Flt3L) reverses the features of allergic airway inflammation and increases a Th2-suppressive regulatory lung CD11c highCD11blow dendritic cell (DC) subset in a mouse model. We examined the migratory pattern and Ag uptake efficiency of lung DC subsets in the therapeutic effect of Flt3L. Lung CD11chighCD11blow and CD11clowCD11bhigh DCs from PBS-treated, OVA-sensitized, and Flt3L-treated/OVA-sensitized BALB/c mice were sorted using MACS and FACS for phenotype analysis. Lymphatic chemokine expression in thoracic lymph nodes was determined by immunohistochemistry. Migration of two lung DC subsets to lymphatic chemokines was examined in vitro using a Transwell chemotaxis assay. Labeled Ag was intranasally delivered into mouse lung to track the migration and Ag uptake of lung DCs. The in vitro cytokine secretion of mediastinal lymph node cells was determined using ELISA. CD11c lowCD11bhigh DCs have higher expression of CCR5, CCR6, and CCR7, but lower expression of CCR2 than CD11chighCD11blow DCs. CD11clowCD11bhigh DCs in Flt3L-treated/OVA- sensitized mice demonstrated a less mature phenotype, inefficiency in Ag uptake, and impaired migration in vitro to lymphatic chemokine than those in OVA-sensitized mice. Administration of Flt3L decreased the expression of CCR5 and CCR7 in CD11clowCD11bhigh DCs in OVA-sensitized mice. Fewer Ag-carrying cells were detected in the lungs and lymph nodes in Flt3L-treated/OVA-sensitized mice than OVA-sensitized mice with a greater decrease in CD11clowCD11bhigh DCs. Mediastinal lymph node cells from Flt3L-treated mice secreted higher levels of Th1 cytokines and IL-10 than OVA-sensitized mice in vitro. In conclusion, Flt3L-generated lung immunogenic CD11clowCD11bhigh DCs have a less mature phenotype, impaired Ag uptake, and impaired migration to draining lymph nodes.
| Original language | English |
|---|---|
| Pages (from-to) | 7531-7538 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 183 |
| Issue number | 11 |
| DOIs | |
| State | Published - Dec 1 2009 |
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All Science Journal Classification (ASJC) codes
- Immunology
- Medicine(all)
Cite this
Fms-like tyrosine kinase 3 ligand regulates migratory pattern and antigen uptake of lung dendritic cell subsets in a murine model of allergic airway inflammation. / Shao, Zhifei; Makinde, Toluwalope O.; McGee, Halvor S.; Wang, Xiang; Agrawal, Devendra K.
In: Journal of Immunology, Vol. 183, No. 11, 01.12.2009, p. 7531-7538.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fms-like tyrosine kinase 3 ligand regulates migratory pattern and antigen uptake of lung dendritic cell subsets in a murine model of allergic airway inflammation
AU - Shao, Zhifei
AU - Makinde, Toluwalope O.
AU - McGee, Halvor S.
AU - Wang, Xiang
AU - Agrawal, Devendra K.
PY - 2009/12/1
Y1 - 2009/12/1
N2 - Fms-like tyrosine kinase 3 ligand (Flt3L) reverses the features of allergic airway inflammation and increases a Th2-suppressive regulatory lung CD11c highCD11blow dendritic cell (DC) subset in a mouse model. We examined the migratory pattern and Ag uptake efficiency of lung DC subsets in the therapeutic effect of Flt3L. Lung CD11chighCD11blow and CD11clowCD11bhigh DCs from PBS-treated, OVA-sensitized, and Flt3L-treated/OVA-sensitized BALB/c mice were sorted using MACS and FACS for phenotype analysis. Lymphatic chemokine expression in thoracic lymph nodes was determined by immunohistochemistry. Migration of two lung DC subsets to lymphatic chemokines was examined in vitro using a Transwell chemotaxis assay. Labeled Ag was intranasally delivered into mouse lung to track the migration and Ag uptake of lung DCs. The in vitro cytokine secretion of mediastinal lymph node cells was determined using ELISA. CD11c lowCD11bhigh DCs have higher expression of CCR5, CCR6, and CCR7, but lower expression of CCR2 than CD11chighCD11blow DCs. CD11clowCD11bhigh DCs in Flt3L-treated/OVA- sensitized mice demonstrated a less mature phenotype, inefficiency in Ag uptake, and impaired migration in vitro to lymphatic chemokine than those in OVA-sensitized mice. Administration of Flt3L decreased the expression of CCR5 and CCR7 in CD11clowCD11bhigh DCs in OVA-sensitized mice. Fewer Ag-carrying cells were detected in the lungs and lymph nodes in Flt3L-treated/OVA-sensitized mice than OVA-sensitized mice with a greater decrease in CD11clowCD11bhigh DCs. Mediastinal lymph node cells from Flt3L-treated mice secreted higher levels of Th1 cytokines and IL-10 than OVA-sensitized mice in vitro. In conclusion, Flt3L-generated lung immunogenic CD11clowCD11bhigh DCs have a less mature phenotype, impaired Ag uptake, and impaired migration to draining lymph nodes.
AB - Fms-like tyrosine kinase 3 ligand (Flt3L) reverses the features of allergic airway inflammation and increases a Th2-suppressive regulatory lung CD11c highCD11blow dendritic cell (DC) subset in a mouse model. We examined the migratory pattern and Ag uptake efficiency of lung DC subsets in the therapeutic effect of Flt3L. Lung CD11chighCD11blow and CD11clowCD11bhigh DCs from PBS-treated, OVA-sensitized, and Flt3L-treated/OVA-sensitized BALB/c mice were sorted using MACS and FACS for phenotype analysis. Lymphatic chemokine expression in thoracic lymph nodes was determined by immunohistochemistry. Migration of two lung DC subsets to lymphatic chemokines was examined in vitro using a Transwell chemotaxis assay. Labeled Ag was intranasally delivered into mouse lung to track the migration and Ag uptake of lung DCs. The in vitro cytokine secretion of mediastinal lymph node cells was determined using ELISA. CD11c lowCD11bhigh DCs have higher expression of CCR5, CCR6, and CCR7, but lower expression of CCR2 than CD11chighCD11blow DCs. CD11clowCD11bhigh DCs in Flt3L-treated/OVA- sensitized mice demonstrated a less mature phenotype, inefficiency in Ag uptake, and impaired migration in vitro to lymphatic chemokine than those in OVA-sensitized mice. Administration of Flt3L decreased the expression of CCR5 and CCR7 in CD11clowCD11bhigh DCs in OVA-sensitized mice. Fewer Ag-carrying cells were detected in the lungs and lymph nodes in Flt3L-treated/OVA-sensitized mice than OVA-sensitized mice with a greater decrease in CD11clowCD11bhigh DCs. Mediastinal lymph node cells from Flt3L-treated mice secreted higher levels of Th1 cytokines and IL-10 than OVA-sensitized mice in vitro. In conclusion, Flt3L-generated lung immunogenic CD11clowCD11bhigh DCs have a less mature phenotype, impaired Ag uptake, and impaired migration to draining lymph nodes.
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UR - http://www.scopus.com/inward/citedby.url?scp=73349116588&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0901341
DO - 10.4049/jimmunol.0901341
M3 - Article
C2 - 19917684
AN - SCOPUS:73349116588
VL - 183
SP - 7531
EP - 7538
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 11
ER -