We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Cytokine-dependent regulation of dendritic cell differentiation in the splenic microenvironment.
- Authors
Globisch, Theresa; Steiner, Nancy; Fülle, Lorenz; Lukacs‐Kornek, Veronika; Degrandi, Daniel; Dresing, Philipp; Alferink, Judith; Lang, Roland; Pfeffer, Klaus; Beyer, Marc; Weighardt, Heike; Kurts, Christian; Ulas, Thomas; Schultze, Joachim L.; Förster, Irmgard
- Abstract
The 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 LPS, CCL17 is not expressed in resident splenic DCs as opposed to CD8α−CD11b+ LN DCs, which produce large amounts of CCL17 in particular after maturation. Upon systemic NKT cell activation through α-galactosylceramide stimulation however, CCL17 can be upregulated in both CD8α− and CD8α+ splenic DC subsets and enhances cross-presentation of exogenous antigens. Based on genome-wide expression profiling, we now show that splenic CD11b+ DCs are susceptible to IFN-γ-mediated suppression of CCL17, whereas LN CD11b+CCL17+ DCs downregulate the IFN-γR and are much less responsive to IFN-γ. Under inflammatory conditions, particularly in the absence of IFN-γ signaling in IFN-γRKO mice, CCL17 expression is strongly induced in a major proportion of splenic DCs by the action of GM-CSF in concert with 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.
- Publication
European Journal of Immunology, 2014, Vol 44, Issue 2, p500
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201343820