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*
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan; and
Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases and
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Autocrine activation of APC by IL-12 has recently been revealed; we
demonstrate here that inducible expression of Stat4 in APC is central
to this process. Stat4 is induced in dendritic cells (DC) in a
maturation-dependent manner and in macrophages in an
activation-dependent manner. Stat4 levels directly correlate with
IL-12-dependent IFN-
production by APC as well as IFN- production
by DC during Ag presentation. The Th2 cytokines IL-4 and IL-10 suppress
Stat4 induction in DC and macrophages when present during maturation
and activation, respectively, diminishing IFN- production. In
contrast, IL-4 has no effect on Stat4 levels in mature DC and actually
augments IFN- production by DC during Ag presentation, indicating
that IL-4 acts differently in a spatiotemporal manner. The functional
importance of Stat4 is evident in Stat4-/- DC and
macrophages, which fail to produce IFN-. Furthermore,
Stat4-/- macrophages are defective in NO production in
response to IL-12 and are susceptible to Toxoplasma.
Autocrine IL-12 signaling is required for high-level IFN- production
by APC at critical stages in both innate and adaptive immunity, and the
control of Stat4 expression is likely an important regulator of this
process.
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E. Kuroda, T. Kito, and U. Yamashita Reduced Expression of STAT4 and IFN-{gamma} in Macrophages from BALB/c Mice J. Immunol., June 1, 2002; 168(11): 5477 - 5482. [Abstract] [Full Text] [PDF]
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A. A. Lighvani, D. M. Frucht, D. Jankovic, H. Yamane, J. Aliberti, B. D. Hissong, B. V. Nguyen, M. Gadina, A. Sher, W. E. Paul, et al. T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells PNAS, December 18, 2001; 98(26): 15137 - 15142. [Abstract] [Full Text] [PDF]
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A. Gigliotti Rothfuchs, D. Gigliotti, K. Palmblad, U. Andersson, H. Wigzell, and M. E. Rottenberg IFN-{alpha}{beta}-Dependent, IFN-{gamma} Secretion by Bone Marrow-Derived Macrophages Controls an Intracellular Bacterial Infection J. Immunol., December 1, 2001; 167(11): 6453 - 6461. [Abstract] [Full Text] [PDF]
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