A fusion protein composed of IL-2 and caspase-3 ameliorates the outcome of experimental inflammatory colitis

Yuval Sagiv*, Ayelet Kaminitz, Haya Lorberboum-Galski, Nadir Askenasy, Shai Yarkoni

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

8 Scopus citations

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.

Original languageAmerican English
Title of host publicationContemporary Challenges in Autoimmunity
PublisherBlackwell Publishing Inc.
Pages791-797
Number of pages7
ISBN (Print)9781573317627
DOIs
StatePublished - Sep 2009

Publication series

NameAnnals of the New York Academy of Sciences
Volume1173
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Apoptosis
  • Inflamatory bowel disease
  • T cell

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