Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-4-14
pubmed:abstractText
CD4(+) T cells play critical roles in the generation of protective immunity against a variety of pathogens. The main two types of effector CD4(+) T cells, Th1 and Th2 are characterized by their ability to produce signature cytokines. Among them, IL-10 is a multi-functional cytokine that plays a crucial role in maintaining the balance between immunity and tolerance. Although IL-10 is produced by both differentiated primary Th1 and Th2 cells, Th2 cells produce much higher levels of IL-10 upon stimulation. However, little information is available on the molecular mechanisms of IL-10 gene regulation at the transcriptional level. Interferon regulatory factor IRF4 is a member of the IRF family of transcription factors and plays critical roles in the development of CD4(+) T cells into Th2 cells. In this present study, we elucidate the underlying mechanism of IRF4 mediated IL-10 gene transcription in primary CD4(+) T cells. Th2 specific binding of IRF4 to the IRF4 responsive elements in IL-10 locus potentiated IL-10 expression in Th2 cells. Knockdown of IRF4 by siRNA decreased IL-10 expression level in Th2 cells. Nuclear translocation of IRF4 was much higher in Th2 cells upon stimulation, which contribute to maintain IL-10(high) phenotype of Th2 cells. Collectively, our results suggest that stimulation driven quantitative differences of IRF4 in the nucleus and its binding to IL-10 regulatory elements are crucial mechanisms to induce IL-10(high) gene expression in Th2 cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1090-2163
pubmed:author
pubmed:copyrightInfo
2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
268
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
97-104
pubmed:meshHeading
pubmed-meshheading:21440248-Animals, pubmed-meshheading:21440248-Blotting, Western, pubmed-meshheading:21440248-Cell Differentiation, pubmed-meshheading:21440248-Cell Line, Tumor, pubmed-meshheading:21440248-Cell Nucleus, pubmed-meshheading:21440248-Flow Cytometry, pubmed-meshheading:21440248-Gene Expression Regulation, pubmed-meshheading:21440248-HEK293 Cells, pubmed-meshheading:21440248-Humans, pubmed-meshheading:21440248-Interferon Regulatory Factors, pubmed-meshheading:21440248-Interleukin-10, pubmed-meshheading:21440248-Mice, pubmed-meshheading:21440248-Mice, Inbred C57BL, pubmed-meshheading:21440248-Mice, Knockout, pubmed-meshheading:21440248-RNA, pubmed-meshheading:21440248-RNA, Small Interfering, pubmed-meshheading:21440248-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21440248-Specific Pathogen-Free Organisms, pubmed-meshheading:21440248-Th2 Cells, pubmed-meshheading:21440248-Transcription, Genetic
pubmed:year
2011
pubmed:articleTitle
IRF4 regulates IL-10 gene expression in CD4(+) T cells through differential nuclear translocation.
pubmed:affiliation
School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't