In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 26 ( 2002-12-24), p. 16951-16956
Abstract:
Epstein–Barr virus-induced gene 3 (EBI3) is a widely expressed IL-12p40-related protein that associates as a heterodimer with either IL-12p35 or an IL-12p35 homologue, p28, to create a new cytokine (IL-27). To define the function of EBI3 in vivo , we generated knockout mice in which the ebi3 gene was targeted by homologous recombination. EBI3 −/− mice exhibited normal numbers of both naive and mature CD4 + and CD8 + T cells and B cells, but markedly decreased numbers of invariant natural killer T cells (iNKT) as defined by staining with an α-galactosylceramide (αGalCer)-loaded CD1d-tetramer. iNKT cells from EBI3 −/− mice exhibited decreased IL-4 and, to a lesser extent, IFN-γ production after αGalCer stimulation in vitro . A sustained decrease in IL-4 production was also observed in EBI3 −/− mice after αGalCer stimulation in vivo in contrast to IFN-γ production, which was only transiently decreased under such stimulation. Notably, EBI3 −/− mice were resistant to the induction of immunopathology associated with oxazolone-induced colitis, a colitis model mediated primarily by T helper (Th) 2-type cytokine production by iNKT cells. In contrast, trinitrobenzene sulfonic acid-induced colitis, a predominantly Th1-mediated colitis model, was unaffected. Thus, EBI3 plays a critical regulatory role in the induction of Th2-type immune responses and the development of Th2-mediated tissue inflammation in vivo , which may be mediated through the control of iNKT cell function.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.252648899
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2002
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
