A fusion protein composed of IL-2 and caspase-3 ameliorates the outcome of experimental inflammatory colitis.
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.
Sagiv
Yuval
Y
Target-In Ltd, Petach Tikva, Israel.
Kaminitz
Ayelet
A
Lorberboum-Galski
Haya
H
Askenasy
Nadir
N
Yarkoni
Shai
S
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D016264:Dextran Sulfate; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; D016264:Dextran Sulfate; D053148:Caspase 3