Abstract:
:Targeted depletion of immune cells expressing the interleukin-2 (IL-2) receptor can exacerbate inflammatory bowel disease (IBD) through elimination of regulatory T (Treg) cells, or ameliorate its course by depletion of cytotoxic cells. To answer this question we used a fusion protein composed of IL-2 and caspase-3 (IL2-cas) in an experimental model of DSS-induced toxic colitis. In a preventive setting, co-administration of DSS with a daily therapeutic dose of IL2-cas for seven days improved all disease parameters. Although CD4(+)CD25(+) T cells were depleted in the mesenteric lymph nodes, a fractional increase in CD4(+)FoxP3(+) T cells was observed in the spleen. Likewise, IL2-cas therapy improved the outcome of established disease in a chronic model of colitis. These data demonstrate that therapies that use IL-2 as a targeting moiety exert a protective effect over the colon under conditions of inflammation. The efficacy of IL-2-targeted therapy is attributed to reduced activity of reactive T cells, which ameliorates the secondary inflammatory infiltration. IL2-cas evolves as a potential therapeutic tool in IBD.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Sagiv Y,Kaminitz A,Lorberboum-Galski H,Askenasy N,Yarkoni Sdoi
10.1111/j.1749-6632.2009.04877.xsubject
Has Abstractpub_date
2009-09-01 00:00:00pages
791-7eissn
0077-8923issn
1749-6632pii
NYAS4877journal_volume
1173pub_type
杂志文章abstract::The large-scale differential gene expression in lymphomononuclear cells of six patients with recently diagnosed type), and six normal individuals matched to patients for sex and age were studied. Glass slides containing 4608 cDNAs from the IMAGE library were spotted using robotic technology. Statistical analysis was c...
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journal_title:Annals of the New York Academy of Sciences
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