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CD70 antibody therapy for the prevention and treatment of experimental Inflammatory Bowel Disease (IBD).
Author(s) -
Manocha Monika,
Rietdijk Svend,
Laouar Amale,
Bhan Atul,
Terhost Cox,
Swamy Manjunath N
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.859.10
Subject(s) - immunology , colitis , proinflammatory cytokine , inflammatory bowel disease , lamina propria , medicine , antibody , inflammation , tumor necrosis factor alpha , cytokine , t cell , disease , immune system , pathology , epithelium
Background Inflammatory bowel disease is a chronic disorder of the gastrointestinal tract, characterized by an aberrant mucosal T cell‐mediated inflammation. The costimulatory molecule CD70 is constitutively expressed by a unique antigen presenting cell in the lamina propria and its interaction with T cells is critical for the gut mucosal T cell activation. Objective To test if blockade of CD70 reduces intestinal inflammation in an experimental model of colitis Methods Colitis was induced by adoptively transferring CD45RB hi CD4 + T cells into Rag 1 −/− mice, the mice were treated with control Ig or a blocking anti‐CD70 antibody twice weekly for 6‐8 weeks and the animals were monitored for disease development. Results Treatment with CD70 blocking antibody dramatically reduced the colitis‐associated weight loss, clinical symptoms and intestinal hisopathology. Importantly, anti‐CD70 antibody treatment initiated after onset of the disease was also able to partially reverse the features of colitis. The Th‐1 related cytokine IFNγ as well as key proinflammatory cytokines of the Th17 pathway, including IL‐23, IL‐17, IL‐6, and TNFα were significantly reduced after CD70 antibody treatment as compared to control group (p<0.001). Conclusion: This study shows that both Th1 and Th17 related cytokines play a dominant role in the pathogenesis of IBD and that CD70 blockade can effectively suppress these cytokines leading to reduction of inflammation. Source of Research support Crohn's and Colitis foundation of America (CCFA)