Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2007-10-30
pubmed:abstractText
Epstein-Barr virus-induced gene 3 (EBI3) and the p35 subunit of IL-12 have been reported to form a heterodimeric hematopoietin in human and mouse. We have constructed a heterodimeric protein covalently linking EBI3 and p35, to form a novel cytokine which we now call IL-35. The Fc fusion protein of IL-35 induced proliferation of murine CD4(+)CD25(+) and CD4(+)CD25(-) T cells when stimulated with immobilized anti-CD3 and anti-CD28 antibodies in vitro. The IL-35-expanded CD4(+)CD25(+) T cell population expressed Foxp3 and produced elevated levels of IL-10, whereas the IL-35-induced CD4(+)CD25(-) T cells produced IFN-gamma but not IL-4. The in vitro expanded CD4(+)CD25(+) T cells retained their suppressive functions against CD4(+)CD25(-) effector cells. Furthermore, when cultured with soluble anti-CD3 antibody and antigen-presenting cells, IL-35 suppressed the proliferation of CD4(+)CD25(-) effector cells. Moreover, IL-35 inhibited the differentiation of Th17 cells in vitro. In vivo, IL-35 effectively attenuated established collagen-induced arthritis in mice, with concomitant suppression of IL-17 production but enhanced IFN-gamma synthesis. Thus, IL-35 is a novel anti-inflammatory cytokine suppressing the immune response through the expansion of regulatory T cells and suppression of Th17 cell development.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3021-9
pubmed:meshHeading
pubmed-meshheading:17874423-Animals, pubmed-meshheading:17874423-Arthritis, Experimental, pubmed-meshheading:17874423-Blotting, Western, pubmed-meshheading:17874423-Cell Differentiation, pubmed-meshheading:17874423-Cell Proliferation, pubmed-meshheading:17874423-Humans, pubmed-meshheading:17874423-Interleukin-12 Subunit p35, pubmed-meshheading:17874423-Interleukins, pubmed-meshheading:17874423-Lymphocyte Activation, pubmed-meshheading:17874423-Male, pubmed-meshheading:17874423-Mice, pubmed-meshheading:17874423-Mice, Inbred BALB C, pubmed-meshheading:17874423-Mice, Inbred DBA, pubmed-meshheading:17874423-Recombinant Proteins, pubmed-meshheading:17874423-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17874423-T-Lymphocyte Subsets, pubmed-meshheading:17874423-T-Lymphocytes, Regulatory
pubmed:year
2007
pubmed:articleTitle
IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells.
pubmed:affiliation
Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't