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231224s2015 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2015.01.006
|2 doi
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|a pubmed24n0819.xml
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|a (DE-627)NLM245821260
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|a (NLM)25638413
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|a (PII)S1521-6616(15)00025-X
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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|a Qiao, Guilin
|e verfasserin
|4 aut
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|a A77 1726, the active metabolite of leflunomide, attenuates lupus nephritis by promoting the development of regulatory T cells and inhibiting IL-17-producing double negative T cells
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|c 2015
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Completed 29.06.2015
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|a Date Revised 03.12.2021
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2015 Elsevier Inc. All rights reserved.
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|a Lupus nephritis (LN) is a challenging problem that affects 50% of patients with systemic lupus erythematosus (SLE) without effective therapy. Here, we report that A77 1726, the active metabolite of leflunomide, effectively inhibits development of LN and attenuates the generalized autoimmune features. A77 1726 suppresses the expansion of double negative (DN) T cells, and inhibits T and B cell activation. Intriguingly, A77 1726 treatment significantly increases CD4(+)Foxp3(+) regulatory T cells but suppresses potential "pathogenic" IL-17-producing DN T cells in lymph nodes. In vitro experiment shows that A77 1726 potentiates the conversion of naive CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(+) inducible regulatory T cells (iTregs) by inhibiting Akt. Taken together, our data indicate that the therapeutic effects of A77 1726 in murine LN are mediated, at least in part, by augmenting iTregs which suppress pathogenic IL-17-producing DN T cells through an Akt-dependent mechanism
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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|a Double negative T cells
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|a IL-17
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|a Leflunomide
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|a Lupus nephritis
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|a Regulatory T cells
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|a Systemic lupus erythematosus
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|a Aniline Compounds
|2 NLM
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|a Antibodies, Antinuclear
|2 NLM
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|a Crotonates
|2 NLM
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|a Hydroxybutyrates
|2 NLM
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|a Immunosuppressive Agents
|2 NLM
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|a Interleukin-17
|2 NLM
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|a Nitriles
|2 NLM
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|a Toluidines
|2 NLM
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|a teriflunomide
|2 NLM
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|a 1C058IKG3B
|2 NLM
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|a Proto-Oncogene Proteins c-akt
|2 NLM
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|a EC 2.7.11.1
|2 NLM
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1 |
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|a Yang, Lifen
|e verfasserin
|4 aut
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1 |
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|a Li, Zhenping
|e verfasserin
|4 aut
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1 |
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|a Williams, James W
|e verfasserin
|4 aut
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|a Zhang, Jian
|e verfasserin
|4 aut
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773 |
0 |
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|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 157(2015), 2 vom: 15. Apr., Seite 166-74
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
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|g volume:157
|g year:2015
|g number:2
|g day:15
|g month:04
|g pages:166-74
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|u http://dx.doi.org/10.1016/j.clim.2015.01.006
|3 Volltext
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|a AR
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|d 157
|j 2015
|e 2
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|h 166-74
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