RGD Reference Report - 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. - Rat Genome Database

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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.

Authors: Shao, Z  Makinde, TO  McGee, HS  Wang, X  Agrawal, DK 
Citation: Shao Z, etal., J Immunol. 2009 Dec 1;183(11):7531-8. doi: 10.4049/jimmunol.0901341. Epub 2009 Nov 16.
RGD ID: 8549811
Pubmed: PMID:19917684   (View Abstract at PubMed)
DOI: DOI:10.4049/jimmunol.0901341   (Journal Full-text)

Fms-like tyrosine kinase 3 ligand (Flt3L) reverses the features of allergic airway inflammation and increases a Th2-suppressive regulatory lung CD11c(high)CD11b(low) 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 CD11c(high)CD11b(low) and CD11c(low)CD11b(high) 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(low)CD11b(high) DCs have higher expression of CCR5, CCR6, and CCR7, but lower expression of CCR2 than CD11c(high)CD11b(low) DCs. CD11c(low)CD11b(high) 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 CD11c(low)CD11b(high) 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 CD11c(low)CD11b(high) 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 CD11c(low)CD11b(high) DCs have a less mature phenotype, impaired Ag uptake, and impaired migration to draining lymph nodes.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCR2Humanasthma  ISOCcr2 (Mus musculus)protein:increased expression:lung and dendritic cell (mouse)RGD 
CCR6Humanasthma  ISOCcr6 (Mus musculus)protein:increased expression:lung and dendritic cell (mouse)RGD 
CCR7Humanasthma  ISOCcr7 (Mus musculus)protein:increased expression:lung and dendritic cell (mouse)RGD 
Ccr2Ratasthma  ISOCcr2 (Mus musculus)protein:increased expression:lung and dendritic cell (mouse)RGD 
Ccr2Mouseasthma  IEP protein:increased expression:lung and dendritic cell (mouse)RGD 
Ccr6Ratasthma  ISOCcr6 (Mus musculus)protein:increased expression:lung and dendritic cell (mouse)RGD 
Ccr6Mouseasthma  IEP protein:increased expression:lung and dendritic cell (mouse)RGD 
Ccr7Ratasthma  ISOCcr7 (Mus musculus)protein:increased expression:lung and dendritic cell (mouse)RGD 
Ccr7Mouseasthma  IEP protein:increased expression:lung and dendritic cell (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr2  (C-C motif chemokine receptor 2)
Ccr6  (C-C motif chemokine receptor 6)
Ccr7  (C-C motif chemokine receptor 7)

Genes (Mus musculus)
Ccr2  (C-C motif chemokine receptor 2)
Ccr6  (C-C motif chemokine receptor 6)
Ccr7  (C-C motif chemokine receptor 7)

Genes (Homo sapiens)
CCR2  (C-C motif chemokine receptor 2)
CCR6  (C-C motif chemokine receptor 6)
CCR7  (C-C motif chemokine receptor 7)


Additional Information