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Pharmacological mod...
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Huang, Yi ShuKennedy Institute of Rheumatology,Chang Gung Memorial Hospital
(author)
Pharmacological modulation of T cell immunity results in long-term remission of autoimmune arthritis
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2021-05-03
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Proceedings of the National Academy of Sciences,2021
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:d8b2c634-7c00-47e3-8013-58d0e2be886b
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https://lup.lub.lu.se/record/d8b2c634-7c00-47e3-8013-58d0e2be886bURI
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https://doi.org/10.1073/pnas.2100939118DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Chronic inflammatory diseases like rheumatoid arthritis are characterized by a deficit in fully functional regulatory T cells. DNA-methylation inhibitors have previously been shown to promote regulatory T cell responses and, in the present study, we evaluated their potential to ameliorate chronic and acute animal models of rheumatoid arthritis. Of the drugs tested, decitabine was the most effective, producing a sustained therapeutic effect that was dependent on indoleamine 2,3-dioxygenase (IDO) and was associated with expansion of induced regulatory T cells, particularly at the site of disease activity. Treatment with decitabine also caused apoptosis of Th1 and Th17 cells in active arthritis in a highly selective manner. The molecular basis for this selectivity was shown to be ENT1, a nucleoside transporter, which facilitates intracellular entry of the drug and is up-regulated on effector T cells during active arthritis. It was further shown that short-term treatment with decitabine resulted in the generation of a population of regulatory T cells that were able to suppress arthritis upon adoptive transfer. In summary, a therapeutic approach using an approved drug is described that treats active inflammatory disease effectively and generates robust regulatory T cells with the IDO-dependent capacity to maintain remission.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Tseng, Wen YiKennedy Institute of Rheumatology,Chang Gung University,Chang Gung Memorial Hospital
(author)
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Clanchy, Felix I.L.University of Oxford,Kennedy Institute of Rheumatology
(author)
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Topping, Louise M.Kennedy Institute of Rheumatology
(author)
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Ogbechi, JoyKennedy Institute of Rheumatology
(author)
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McNamee, KayKennedy Institute of Rheumatology
(author)
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Perocheau, DanyKennedy Institute of Rheumatology
(author)
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Chiang, Nien YiKennedy Institute of Rheumatology
(author)
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Ericsson, PeterLund University,Lunds universitet,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Rausing laboratory of Lund - Tumor section,Lund University Research Groups(Swepub:lu)farm-per
(author)
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Sundstedt, AnetteLund University,Lunds universitet,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Rausing laboratory of Lund - Tumor section,Lund University Research Groups(Swepub:lu)an3586su
(author)
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Xue, Zhong TianSkåne University Hospital
(author)
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Salford, Leif G.Lund University,Lunds universitet,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Rausing laboratory of Lund - Tumor section,Lund University Research Groups(Swepub:lu)nkir-lsa
(author)
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Sjögren, Hans OlovLund University,Lunds universitet,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Rausing laboratory of Lund - Tumor section,Lund University Research Groups(Swepub:lu)wbl-hos
(author)
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Stone, Trevor W.Kennedy Institute of Rheumatology
(author)
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Lin, Hsi HsienChang Gung Memorial Hospital,Chang Gung University
(author)
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Luo, Shue FenChang Gung Memorial Hospital
(author)
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Williams, Richard O.Kennedy Institute of Rheumatology
(author)
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Kennedy Institute of RheumatologyChang Gung Memorial Hospital
(creator_code:org_t)
Related titles
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In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences118:191091-6490
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In:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences118:190027-8424
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Huang, Yi Shu
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Tseng, Wen Yi
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Clanchy, Felix I ...
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Topping, Louise ...
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Ogbechi, Joy
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McNamee, Kay
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Perocheau, Dany
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Chiang, Nien Yi
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Ericsson, Peter
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Sundstedt, Anett ...
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Xue, Zhong Tian
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Salford, Leif G.
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Sjögren, Hans Ol ...
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Stone, Trevor W.
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Lin, Hsi Hsien
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Luo, Shue Fen
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Williams, Richar ...
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