Journal article
Selective Activation of Tumor Necrosis Factor Receptor II Induces Antiinflammatory Responses and Alleviates Experimental Arthritis
Arthritis & rheumatology (Hoboken, N.J.), v 70(5), pp 722-735
01 May 2018
PMID: 29342501
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Objective. Treg cells modulate immune responses and can suppress the development of autoimmune diseases. Tumor necrosis factor receptor II (TNFRII) has been recognized as a key receptor on these cells that facilitates expansion and stabilization of CD4+ Treg cells. The purpose of the present study was to investigate the therapeutic activity of a novel TNFRII agonist in experimental arthritis as well as the role of different Treg cell subsets.
Methods. A novel mouse TNFRII-selective fusion protein (EHD2-sc-mTNF(R2)) was generated by genetic engineering. Mouse T cells were incubated together with interleukin-2 and/or EHD2-sc-mTNF(R2), and the effects on Treg cells were analyzed by flow cytometry. Mice with collagen-induced arthritis (CIA) were treated with EHD2-sc-mTNF(R2) or saline, and the therapeutic effects were monitored and characterized.
Results. Selective activation of TNFRII was found to expand both CD4+ and CD8+ Treg cells. Moreover, TNFRII activation elevated the number of CD4+CD25+ and CD8+CD25+ Treg cells and increased the number of FoxP3-expressing cells in CD8+, but not CD4+, Treg cells, indicating different mechanisms of TNFRII-induced expansion of diverse T cell subsets with suppressive activity. In the CIA model, we demonstrated that administration of the TNFRII agonist EHD2-sc-mTNF(R2) led to the expansion of both CD4+ and CD8+ Treg cells invivo and induced anti-inflammatory responses that alleviated arthritis.
Conclusion. Our findings support the use of TNFRII-selective therapeutics as an effective approach to the treatment of arthritic disease and possibly other inflammatory and autoimmune diseases.
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Details
- Title
- Selective Activation of Tumor Necrosis Factor Receptor II Induces Antiinflammatory Responses and Alleviates Experimental Arthritis
- Creators
- Roman Fischer - Drexel UniversityMarcel Proske - Drexel UniversityMaelle Duffey - Drexel UniversityHubert Stangl - University Hospital RegensburgGeorge F. Martinez - Drexel UniversityNathalie Peters - Drexel UniversityAlexandra Kraske - Drexel UniversityRainer H. Straub - University Hospital RegensburgJohn R. Bethea - Drexel UniversityRoland E. Kontermann - Drexel UniversityKlaus Pfizenmaier - Drexel University
- Publication Details
- Arthritis & rheumatology (Hoboken, N.J.), v 70(5), pp 722-735
- Publisher
- Wiley
- Number of pages
- 14
- Grant note
- Az. 0563-2.8./508/2 / Carl Zeiss Foundation FI 2138/1-1; STR 511/26-1; STR 511/34-1 / DFG; German Research Foundation (DFG); European Commission
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000430912600011
- Scopus ID
- 2-s2.0-85043478894
- Other Identifier
- 991019168739204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Rheumatology