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PMID: 10993913 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells.

The Journal of experimental medicine ·Vol. 192 ·No. 6 ·2000-09-18 ·Pages 823-33

Hochrein H, O'Keeffe M, Luft T, Vandenabeele S, Grumont RJ, Maraskovsky E, Shortman K

Abstract

Interleukin (IL)-12 may be secreted as a bioactive T helper type 1 (Th1) cell-inducing heterodimer, as a monomer, or as an antagonistic homodimer. We analyzed the IL-12 produced by mouse splenic dendritic cells (DCs), human thymic DCs, and cultured human monocyte-derived DCs. IL-12 production required both a microbial or T cell-derived stimulus and an appropriate cytokine milieu. The different IL-12 forms were differentially regulated by the cytokines present rather than the stimulus used. IL-4 alone or together with granulocyte/macrophage colony-stimulating factor or interferon gamma effectively enhanced the production of the bioactive heterodimer and selectively reduced the antagonistic homodimer of IL-12. Therefore, IL-4, the major Th2-driving cytokine, provides a negative feedback causing DCs to produce the major Th1-inducing cytokine, bioactive IL-12.

MeSH Terms
Animals Cells, Cultured Dendritic Cells/drug effects,immunology Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology Humans Interferon-gamma/pharmacology Interleukin-12/biosynthesis,genetics Interleukin-4/pharmacology Lipopolysaccharides/pharmacology Mice Mice, Inbred C57BL Monocytes/immunology Recombinant Proteins/pharmacology Spleen/immunology T-Lymphocytes/immunology Thymus Gland/immunology
Chemicals
Lipopolysaccharides Recombinant Proteins Interleukin-12 Interleukin-4 Interferon-gamma Granulocyte-Macrophage Colony-Stimulating Factor
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hochrein H
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.
O'Keeffe M
Luft T
Vandenabeele S
Grumont R J
Maraskovsky E
Shortman K
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.192.6.823
Published
2000-09-18
Pages
823-33
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193283
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.192.6.823 PMC Full Text View journal details
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