NDLI: Regulation of ITAM-positive receptors: role of IL-12 and IL-18

Content Provider	PubMed Central
Author	Ortaldo, John R. Robin, Winkler-pickett Wigginton, Jon Horner, Meagan Bere, Earl W. Mason, Anna T. Bhat, Narayan Cherry, James Sanford, Michael Hodge, Deborah L. Young, Howard A.
Copyright Year	2006
Abstract	Our previous studies have identified mechanisms by which cytokine production, blocked by Ly49G2 receptor cross-linking, can be overridden. In this study we analyzed the regulation of other ITAM-positive receptor signaling on NK, NKT, and T cells and characterized the biochemical pathways involved in this signaling. Our studies demonstrate that cross-linking of NKG2D and NK1.1 results in a synergistic NK IFN-γ response when combined with IL-12 or IL-18. Examination of NKT- and T-cell responses demonstrated that cross-linking of NKG2D and CD3 resulted in potent synergy when combined with IL-12 and, to a lesser degree, with IL-18. We have now found that both the p38 MAP kinase and the ERK-dependent signal transduction pathways are required for the synergistic response. Further mechanistic examination of the synergy indicated a potent up-regulation of total IFN-γ mRNA in the nuclear and the cytoplasmic compartment, but mRNA half-life was not affected. Fifteen minutes of IL-12 pretreatment was sufficient to result in maximal synergistic activation, indicating that the response of the cells to the IL-12 signal was rapid and immediate. Thus, our data demonstrate that multiple convergent signals maximize the innate immune response by triggering complementary biochemical signaling pathways.
Related Links	http://dx.doi.org/10.1182/blood-2005-04-1579
Ending Page	1475
Page Count	8
Starting Page	1468
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	4
Volume Number	107
Language	English
Publisher	© 2006 by The American Society of Hematology
Publisher Date	2006-02-15
Access Restriction	Open
Rights Holder	© 2006 by The American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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