Laquinimod, a quinoline-3-carboxamide, induces type II myeloid cells that modulate central nervous system autoimmunity.
Laquinimod, a quinoline-3-carboxamide, induces type II myeloid cells that modulate central nervous system autoimmunity.
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DOI：
10.1371/journal.pone.0033797
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zamvil SS
中科院分区：
文献类型：
--
作者：
Schulze-Topphoff U;Shetty A;Varrin-Doyer M;Molnarfi N;Sagan SA;Sobel RA;Nelson PA;Zamvil SS
Laquinimod is a novel oral drug that is currently being evaluated for the treatment of relapsing-remitting (RR) multiple sclerosis (MS). Using the animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we examined how laquinimod promotes immune modulation. Oral laquinimod treatment reversed established RR-EAE and was associated with reduced central nervous system (CNS) inflammation, decreased Th1 and Th17 responses, and an increase in regulatory T cells (Treg). In vivo laquinimod treatment inhibited donor myelin-specific T cells from transferring EAE to naive recipient mice. In vivo laquinimod treatment altered subpopulations of myeloid antigen presenting cells (APC) that included a decrease in CD11c+CD11b+CD4+ dendritic cells (DC) and an elevation of CD11bhiGr1hi monocytes. CD11b+ cells from these mice exhibited an anti-inflammatory type II phenotype characterized by reduced STAT1 phosphorylation, decreased production of IL-6, IL-12/23 and TNF, and increased IL-10. In adoptive transfer, donor type II monocytes from laquinimod-treated mice suppressed clinical and histologic disease in recipients with established EAE. As effects were observed in both APC and T cell compartments, we examined whether T cell immune modulation occurred as a direct effect of laquinimod on T cells, or as a consequence of altered APC function. Inhibition of Th1 and Th17 differentiation was observed only when type II monocytes or DC from laquinimod-treated mice were used as APC, regardless of whether myelin-specific T cells were obtained from laquinimod-treated or untreated mice. Thus, laquinimod modulates adaptive T cell immune responses via its effects on cells of the innate immune system, and may not influence T cells directly.
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影响因子：
7.3
作者：
Jönsson, S;Andersson, G;Björk, A
通讯作者：
Björk, A
影响因子：
168.9
作者：
Comi, G.;Pulizzi, A.;Filippi, M.
通讯作者：
Filippi, M.
影响因子：
64.5
作者：
KUCHROO, VK;DAS, MP;GLIMCHER, LH
通讯作者：
GLIMCHER, LH
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.3
作者：
Abdul-Majid, KB;Jirholt, J;Harris, RA
通讯作者：
Harris, RA