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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1100-1109. Prepublished online as a Blood First Edition Paper on April 27, 2004; DOI 10.1182/blood-2003-12-4302. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2003-12-4302v1 104/4/1100    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bhattacharyya, S. Articles by Tisch, R. Search for Related Content PubMed PubMed Citation Articles by Bhattacharyya, S. Articles by Tisch, R. Related Collections Immunobiology Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of IB kinase activity Sandip Bhattacharyya, Pradip Sen, Mark Wallet, Brian Long, Albert S. Baldwin, Jr, and Roland Tisch From the Department of Microbiology and Immunology, School of Medicine, the Lineberger Comprehensive Cancer Center, and the Curriculum in Oral Biology, University of North Carolina at Chapel Hill. Interleukin-10 (IL-10) has potent immunoregulatory effects on the maturation and the antigen-presenting cell (APC) function of dendritic cells (DCs). The molecular basis underlying these effects in DCs, however, is ill defined. It is well established that the transcription factor NF-B is a key regulator of DC development, maturation, and APC function. This study was initiated to determine the effects of IL-10 on the NF-B signaling pathway in immature DCs. IL-10 pretreatment of myeloid DCs cultured from bone marrow resulted in reduced DNA binding and nuclear translocation of NF-B after anti-CD40 antibody or lipopolysaccharide (LPS) stimulation. Furthermore, inhibited NF-B activation was characterized by reduced degradation, phosphorylation, or both of IB and IB but not IB and by reduced phosphorylation of Ser536, located in the trans-activation domain of p65. Notably, IL-10–mediated inhibition of NF-B coincided with suppressed IB kinase (IKK) activity in vitro. Furthermore, IL-10 blocked inducible Akt phosphorylation, and inhibitors of phosphatidylinositol 3-kinase (PI3K) effectively suppressed the activation of Akt, IKK, and NF-B. These findings demonstrate that IL-10 targets IKK activation in immature DCs and that suppressing the PI3K pathway in part mediates blockade of the pathway. 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