Journal
INTERNATIONAL IMMUNOLOGY
Volume 20, Issue 9, Pages 1219-1229Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxn078
Keywords
fibroblast; lipid mediators; lipopolysaccharide; stromal cell; Toll-like receptor
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- National Institute of Biomedical Innovation
- Naito Foundation
- Takeda Science Foundation
- Kato Memorial Foundation
- Suzuken Memorial Foundation
- Japan Intractable Disease Research Foundation
- Mitsubishi Pharma Research Foundation
- Clinical Research Foundation
- Yakult Bioscience Research Foundation
- Princess Takamatsu Cancer Research Fund
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Dendritic cells (DCs) are specialized antigen-presenting cells that play pivotal roles in initiating immune responses. However, DC maturation is usually strongly restricted by the stromal microenvironment, especially in non-lymphoid tissues, such as skin and mucosa. Although suppression of DC maturation by stromal cells has been well documented, the molecular basis of this suppression has not been established. In this study, we examined the role of fibroblasts for DC maturation in vitro. The mouse embryonic fibroblasts (MEFs) strongly suppressed LPS-induced DC maturation. Although suppression of class II MHC and CD40 required DC-MEF contact, soluble factors in the culture supernatant of MEFs were sufficient for the suppression of IL-12 and tumor necrosis factor-a production. Using molecular-size selection and HPLC, we determined that prostaglandin E-2 (PGE(2)) is a major soluble inhibitory factor secreted by MEFs. This was confirmed by the fact that cyclooxygenase inhibitors inhibited the production of the suppressive factor by MEFs. These results suggest that PGE2 is a major soluble factor produced by MEFs for the suppression of inflammatory cytokine production from DCs, while a contact mechanism between MEFs and DCs is required for the suppression to induce T cell-stimulating molecules.
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