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Journal Club

Regulation of the IL-23 and IL-12 by STAT3

Kaveeeta Kav

on 28 April 2010

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Transcript of Journal Club

Double click anywhere & add an idea Regulation of the IL-23 and IL-12 Balance by STAT3 Signaling in the Tumor Microenvironment Marcin Kortylevski et al. Cancer Cell 15, Feb 3, 2009. Introduction
STAT3 IL-23 IL-12 Results 1. Role of STAT3 in the Differential Expression of IL-23 and IL-12 in Tumors 2. Stat 3 directly regulates IL-23/p19 Transcription 3.Stat3 Inhibits NF-kB/c-Rel-Mediated IL-12/p35 Gene expression 4. IL-23R and Stat3 Signaling in Tumor-infiltrating Tregs cell-cycle progression cell survival angiogenesis immune evasion Dendritic cells Macrophages Antitumor immunity IL-10 VGEF p35 p40 Promotes antitumor immunity via activation NK cells T helper cells p40 p19 Promotes tumor angiogenesiss Reduced T cells in tumor Facilitated tumor infiltration of T cells IL-23 IL-12
ELISA assay Conclusion: Stat3 signaling drives IL-23 production from TMacs
while IL-12 TDCs. This effect was specific for the tumor microenvironment. Conclusion1: Stat3 positively regulates
IL-23 at the trancriptional level. Direct transcriptional regulation Luciferase assay chIP analyses Conclusion:NFkB/p65 which is also contitutively
activated in B16 cells participates in IL-23/P19 transcription. Immunosupressive role of Stat3 in myeloid cells Intrinsic Stat3 signaling in Tcells mediates
tumor immunosuppresion?? Role of Stat3 and IL-23 in Tcell physiology Conclusions Stat3 signaling in the tumor microenvironment shifts inflammationfrom an antitumor IL-12 to a tumor enhancing IL-23 program via trancrptional activation of the IL-12 specific gene NFkb-rel and p65 have unique roles in regulating gene expression. IL-23 - an important mediator of procarcinogenesis by Stat3 signaling. Stat 3 Cytokines Immunosupressive factors
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