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Cytokine-dependent dendritic cell differentiation in the splenic microenvironment

ABSTRACT: The dendritic cell (DC)-derived chemokine CCL17, a ligand of CCR4, has been shown to promote various inflammatory diseases such as atopic dermatitis, atherosclerosis, and inflammatory bowel disease. Under steady state conditions, and even after systemic stimulation with lipopolysaccharide, CCL17 is not expressed in resident splenic DC as opposed to CD8-CD11b+ lymph node (LN) DC, which produce large amounts of CCL17, in particular after maturation. Upon systemic NKT cell activation through alpha-galactosylceramide stimulation, however, CCL17 can be upregulated in both CD8- and CD8+ splenic DC subsets and enhances cross-presentation of exogenous antigens. Based on genome wide expression profiling, we now show that splenic DC are susceptible to Interferon-gamma (IFNgamma) mediated suppression of CCL17, whereas LN DC are much less responsive to IFNgamma and downregulate the IFNgamma receptor. Under inflammatory conditions, particularly in the absence of IFNgamma signaling in IFNgamma receptor deficient mice, CCL17 expression is strongly induced in a major proportion of splenic DC by the action of granulocyte-macrophage colony stimulating factor (GM-CSF) in concert with interleukin (IL)-4. Our findings demonstrate that the local cytokine milieu and differential cytokine responsiveness of DC subsets regulate lymphoid organ specific immune responses at the level of chemokine expression.

ORGANISM(S): Mus musculus

PROVIDER: GSE43456 | GEO | 2013/09/19

SECONDARY ACCESSION(S): PRJNA186443

REPOSITORIES: GEO

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Cytokine-dependent dendritic cell differentiation in the splenic microenvironment

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