Details

Autor(en) / Beteiligte

• Zhou, Fang
• Ciric, Bogoljub
• Li, Hongmei
• Yan, Yaping
• Li, Ke
• Cullimore, Melissa
• Lauretti, Elisabetta
• Gonnella, Patricia
• Zhang, Guang‐Xian
• Rostami, Abdolmohamad

Titel

IL‐10 deficiency blocks the ability of LPS to regulate expression of tolerance‐related molecules on dendritic cells

Ist Teil von

• European journal of immunology, 2012-06, Vol.42 (6), p.1449-1458

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Interleukin‐10 (IL‐10) is an anti‐inflammatory cytokine that plays an important role in regulating the local inflammatory immune response, but regulatory mechanisms of this cytokine have not been fully elucidated. Here, we demonstrate that IL‐10 deficiency renders LPS treatment ineffective in regulating the expression of CD40, CD80, CD86, B7‐H2, and B7‐DC on dendritic cells (DCs) and blocks upregulation of IL‐27. This inability to respond to LPS was found in both IL‐10−/− bone marrow derived and splenic DCs. Compared with wild‐type DCs, IL‐10−/– DCs expressed similar levels of TLR4 and CD14, but produced less LPS‐binding protein. The deficiency in LPS‐binding protein production may explain the failure of IL‐10−/− DCs to respond normally to LPS. Moreover, lack of IL‐10 modulated the proportions of CD11c+CD8+ and CD11c+B220+ DCs, which play an important role in local inflammatory responses and tolerance. IL‐10 deficiency also blocked expression of galectin‐1, CD205, and CD103, which are necessary for central and peripheral tolerance. While they did not respond to LPS, IL‐10−/− DCs produced increased levels of IL‐6 and CCL4 after TNF‐α treatment. Together, our results demonstrate that IL‐10 deficiency affects the immune functions of DCs, which may contribute to the increased severity of autoimmune diseases seen in IL‐10−/− mice.