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

Copyright © 2015 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 157(2015), 2 vom: 15. Apr., Seite 166-74
1. Verfasser: Qiao, Guilin (VerfasserIn)
Weitere Verfasser: Yang, Lifen, Li, Zhenping, Williams, James W, Zhang, Jian
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2015
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Double negative T cells IL-17 Leflunomide Lupus nephritis Regulatory T cells Systemic lupus erythematosus Aniline Compounds Antibodies, Antinuclear mehr... Crotonates Hydroxybutyrates Immunosuppressive Agents Interleukin-17 Nitriles Toluidines teriflunomide 1C058IKG3B Proto-Oncogene Proteins c-akt EC 2.7.11.1
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520 |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 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Double negative T cells 
650 4 |a IL-17 
650 4 |a Leflunomide 
650 4 |a Lupus nephritis 
650 4 |a Regulatory T cells 
650 4 |a Systemic lupus erythematosus 
650 7 |a Aniline Compounds  |2 NLM 
650 7 |a Antibodies, Antinuclear  |2 NLM 
650 7 |a Crotonates  |2 NLM 
650 7 |a Hydroxybutyrates  |2 NLM 
650 7 |a Immunosuppressive Agents  |2 NLM 
650 7 |a Interleukin-17  |2 NLM 
650 7 |a Nitriles  |2 NLM 
650 7 |a Toluidines  |2 NLM 
650 7 |a teriflunomide  |2 NLM 
650 7 |a 1C058IKG3B  |2 NLM 
650 7 |a Proto-Oncogene Proteins c-akt  |2 NLM 
650 7 |a EC 2.7.11.1  |2 NLM 
700 1 |a Yang, Lifen  |e verfasserin  |4 aut 
700 1 |a Li, Zhenping  |e verfasserin  |4 aut 
700 1 |a Williams, James W  |e verfasserin  |4 aut 
700 1 |a Zhang, Jian  |e verfasserin  |4 aut 
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773 1 8 |g volume:157  |g year:2015  |g number:2  |g day:15  |g month:04  |g pages:166-74 
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