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

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

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1449-1458
Number of pages10
JournalEuropean Journal of Immunology
Volume42
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Costimulatory molecule · DCs · IL-10 · TLR4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zhou, F., Ciric, B., Li, H., Yan, Y., Li, K., Cullimore, M., Lauretti, E., Gonnella, P., Zhang, G. X., & Rostami, A. (2012). IL-10 deficiency blocks the ability of LPS to regulate expression of tolerance-related molecules on dendritic cells. European Journal of Immunology, 42(6), 1449-1458. https://doi.org/10.1002/eji.201141733