| First Author | Globisch T | Year | 2014 |
| Journal | Eur J Immunol | Volume | 44 |
| Issue | 2 | Pages | 500-10 |
| PubMed ID | 24136200 | Mgi Jnum | J:208732 |
| Mgi Id | MGI:5564876 | Doi | 10.1002/eji.201343820 |
| Citation | Globisch T, et al. (2014) Cytokine-dependent regulation of dendritic cell differentiation in the splenic microenvironment. Eur J Immunol 44(2):500-10 |
| abstractText | 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 CD8alpha(-)CD11b(+) LN DCs, 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 CD8alpha(-) and CD8alpha(+) 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-gamma-mediated suppression of CCL17, whereas LN CD11b(+)CCL17(+) DCs downregulate the IFN-gammaR and are much less responsive to IFN-gamma. Under inflammatory conditions, particularly in the absence of IFN-gamma signaling in IFN-gammaRKO 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. |
