Journal article

Treatment of Arthritis by Macrophage Depletion and Immunomodulation Testing an Apoptosis-Mediated Therapy in a Humanized Death Receptor Mouse Model

Jun Li, Hui-Chen Hsu, PingAr Yang, Qi Wu, Hao Li, Laura E Edgington, Matthew Bogyo, Robert P Kimberly, John D Mountz

ARTHRITIS AND RHEUMATISM | WILEY-BLACKWELL | Published : 2012

Abstract

OBJECTIVE: To determine the therapeutic efficacy and immunomodulatory effect of an anti-human death receptor 5 (DR5) antibody, TRA-8, in eliminating macrophage subsets in a mouse model of type II collagen-induced arthritis (CIA). METHODS: A human/mouse-chimeric DR5-transgenic mouse, under the regulation of a mouse 3-kb promoter and a loxP-flanked STOP cassette, was generated and crossed with an ubiquitous Cre (Ubc.Cre) mouse and a lysozyme M-Cre (LysM.Cre)-transgenic mouse to achieve inducible or macrophage-specific expression. Chicken type II collagen was used to induce CIA in mice, which were then treated with an anti-human DR5 antibody, TRA-8. Clinical scores, histopathologic severity, ma..

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Grants

Awarded by Department of Veterans Affairs


Awarded by NIH


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Awarded by NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING


Awarded by Veterans Affairs


Funding Acknowledgements

Supported by grants from the Lupus Research Institute (to Dr. Hsu) and Daiichi Sankyo (to Dr. Mountz). Additional support was provided by the Arthritis Foundation (Postdoc Fellowship Award to Dr. J. Li), the American College of Rheumatology Research and Education Foundation (Within Our Reach grant), the Alliance for Lupus Research (Target Identification in Lupus grant), the Department of Veterans Affairs (Merit Review grant 1I01BX000600-01), and the NIH (grants R01-AI-083705-01A2 to Dr. Hsu, 1-R01-EB-005011-06 to Dr. Bogyo, 1-AI-071110-01A1 and ARRA-R01-AI-71110-02S1 to Dr. Mountz, P30-AR-048311 to the Rheumatic Diseases Core Centers including Analytical Genomics and Transgenics Core, Comprehensive Flow Cytometry Core, and Analytic Imaging and Immunoreagent Core, and P30-AR-046031 to the Center for Metabolic Bone Disease-Histomorphometry and Molecular Analysis Core).