Antibodies to Complement Receptor 3 Treat Established Inflammation in Murine Models of Colitis and a Novel Model of Psoriasiform Dermatitis

Prior studies indicated the ability of Abs to complement receptor 3 (CR3, CD11b/CD18) to suppress the production of IL-12 from immune cells. Therefore, we tested the ability of an anti-CR3 Ab (clone M1/70) to treat established IL-12-dependent Th1-mediated inflammation in murine models. Systemic admi...

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Bibliographic Details
Published in:Journal of Immunology 2006-11, Vol.177 (10), p.6974-6982
Main Authors: Leon, Francisco, Contractor, Nikhat, Fuss, Ivan, Marth, Thomas, Lahey, Edward, Iwaki, Shoko, la Sala, Andrea, Hoffmann, Victoria, Strober, Warren, Kelsall, Brian L
Format: Article
Language:English
Subjects:
Adoptive Transfer
Animals
Antibodies - administration & dosage
Antibodies - therapeutic use
CD4-Positive T-Lymphocytes - transplantation
Cells, Cultured
Colitis - chemically induced
Colitis - immunology
Colitis - therapy
Dermatitis - immunology
Dermatitis - pathology
Dermatitis - therapy
Disease Models, Animal
Female
Inflammation Mediators - administration & dosage
Inflammation Mediators - therapeutic use
Injections, Intravenous
Macrophage-1 Antigen - immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Nude
Psoriasis - immunology
Psoriasis - pathology
Psoriasis - therapy
Trinitrobenzenesulfonic Acid - toxicity
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Summary:Prior studies indicated the ability of Abs to complement receptor 3 (CR3, CD11b/CD18) to suppress the production of IL-12 from immune cells. Therefore, we tested the ability of an anti-CR3 Ab (clone M1/70) to treat established IL-12-dependent Th1-mediated inflammation in murine models. Systemic administration of anti-CR3 significantly ameliorated established intestinal inflammation following the intrarectal administration of trinitrobenzene sulfonic acid (TNBS-colitis), as well as colitis and skin inflammation in C57BL/10 RAG-2(-/-) mice reconstituted with CD4+CD45RBhigh T cells. The hyperproliferative skin inflammation in this novel murine model demonstrated many characteristics of human psoriasis, and was prevented by the adoptive transfer of CD45RBlow T cells. In vitro and in vivo studies suggest that anti-CR3 treatment may act, at least in part, by directly inhibiting IL-12 production by APCs. Administration of anti-CR3 may be a useful therapeutic approach to consider for the treatment of inflammatory bowel disease and psoriasis in humans.
ISSN:0022-1767
1550-6606
1365-2567
DOI:10.4049/jimmunol.177.10.6974