Inhibition of NKG2D receptor function by antibody therapy attenuates transfer-induced colitis in SCID mice |
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Authors: | Kjellev Stine Haase Claus Lundsgaard Dorthe Ursø Birgitte Tornehave Ditte Markholst Helle |
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Affiliation: | 1. Department of Immunopharmacology, Novo Nordisk a/s, M?l?v, Denmark;2. Hagedorn Research Institute, Gentofte, Denmark;3. Department of Cancer and Immunobiology, Novo Nordisk a/s, M?l?v, Denmark;4. Department of Hemostasis Pharmacology, Novo Nordisk a/s, M?l?v, Denmark |
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Abstract: | A role for the activating NK-receptor NKG2D has been indicated in several autoimmune diseases in humans and in animal models of type 1 diabetes and multiple sclerosis, and treatment with monoclonal antibodies to NKG2D attenuated disease severity in these models. In an adoptive transfer-induced model of colitis, we found a significantly higher frequency of CD4(+)NKG2D(+) cells in blood, mesenteric lymph nodes, colon, and spleen from colitic mice compared to BALB/c donor-mice. We, therefore, wanted to study the effect of anti-NKG2D antibody (CX5) treatment initiated either before onset of colitis, when the colitis was mild, or when severe colitis was established. CX5 treatment decreased the detectable levels of cell-surface NKG2D and prophylactic administration of CX5 attenuated the development of colitis significantly, whereas a more moderate reduction in the severity of disease was observed after CX5 administration to mildly colitic animals. CX5 did not attenuate severe colitis. We conclude that the frequency of CD4(+)NKG2D(+) cells increase during development of experimental colitis. NKG2D may play a role in the early stages of colitis in this model, since early administration of CX5 attenuated disease severity. |
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Keywords: | Adoptive transfer model Colitis Inflammatory bowel disease NKG2D |
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