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Tumor necrosis factor receptor II<\/jats:styled-content> (TNFRII<\/jats:styled-content>) has been recognized as a key receptor on these cells that facilitates expansion and stabilization of CD<\/jats:styled-content>4+ Treg cells. The purpose of the present study was to investigate the therapeutic activity of a novel TNFRII<\/jats:styled-content> agonist in experimental arthritis as well as the role of different Treg cell subsets.<\/jats:p><\/jats:sec>Methods<\/jats:title>A novel mouse TNFRII<\/jats:styled-content>\u2013selective fusion protein (EHD<\/jats:styled-content>2\u2010sc\u2010mTNFR<\/jats:sub><\/jats:styled-content>2<\/jats:sub>) was generated by genetic engineering. Mouse T cells were incubated together with interleukin\u20102 and\/or EHD<\/jats:styled-content>2\u2010sc\u2010mTNFR<\/jats:sub><\/jats:styled-content>2<\/jats:sub>, and the effects on Treg cells were analyzed by flow cytometry. Mice with collagen\u2010induced arthritis (CIA<\/jats:styled-content>) were treated with EHD<\/jats:styled-content>2\u2010sc\u2010mTNFR<\/jats:sub><\/jats:styled-content>2<\/jats:sub> or saline, and the therapeutic effects were monitored and characterized.<\/jats:p><\/jats:sec>Results<\/jats:title>Selective activation of TNFRII<\/jats:styled-content> was found to expand both CD<\/jats:styled-content>4+ and CD<\/jats:styled-content>8+ Treg cells. Moreover, TNFRII<\/jats:styled-content> activation elevated the number of CD<\/jats:styled-content>4+CD<\/jats:styled-content>25+ and CD<\/jats:styled-content>8+CD<\/jats:styled-content>25+ Treg cells and increased the number of FoxP3\u2010expressing cells in CD<\/jats:styled-content>8+, but not CD<\/jats:styled-content>4+, Treg cells, indicating different mechanisms of TNFRII<\/jats:styled-content>\u2010induced expansion of diverse T cell subsets with suppressive activity. In the CIA<\/jats:styled-content> model, we demonstrated that administration of the TNFRII<\/jats:styled-content> agonist EHD<\/jats:styled-content>2\u2010sc\u2010mTNFR<\/jats:sub><\/jats:styled-content>2<\/jats:sub> led to the expansion of both CD<\/jats:styled-content>4+ and CD<\/jats:styled-content>8+ Treg cells in\u00a0vivo and induced antiinflammatory responses that alleviated arthritis.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our findings support the use of TNFRII<\/jats:styled-content>\u2010selective therapeutics as an effective approach to the treatment of arthritic disease and possibly other inflammatory and autoimmune diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40413","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T19:02:45Z","timestamp":1516215765000},"page":"722-735","source":"Crossref","is-referenced-by-count":41,"title":["Selective Activation of Tumor Necrosis Factor Receptor II<\/scp> Induces Antiinflammatory Responses 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