The immunomodulatory effect of laquinimod in CNS autoimmunity is mediated by the aryl hydrocarbon receptor

被引：25
作者：
Berg, Johannes [1 ]
Mahmoudjanlou, Yasaman [1 ]
Duscha, Alexander [1 ]
Massa, Megan G. [1 ]
Thoene, Jan [1 ]
Esser, Charlotte [2 ]
Gold, Ralf [1 ]
Haghikia, Aiden [1 ]
机构：
[1] Ruhr Univ Bochum, Dept Neurol, D-44801 Bochum, Germany
[2] Leibniz Res Inst Environm Med, D-40225 Dusseldorf, Germany
来源：
JOURNAL OF NEUROIMMUNOLOGY | 2016年 / 298卷
关键词：
Laquinimod; Aryl hydrocarbon receptor; Experimental autoimmune encephalomyelitis; Immunomodulation; REGULATORY T-CELLS; REMITTING MULTIPLE-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; NEUROTROPHIC FACTOR; ORAL LAQUINIMOD; IN-VITRO; AH RECEPTOR; B-CELLS; ENCEPHALOMYELITIS; BRAIN;
D O I：
10.1016/j.jneuroim.2016.06.003
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Though several functional properties of laquinimod have been identified, our understanding of the underlying mechanisms is still incomplete. Since the compound elicits similar immunomodulatory effects to ligands of the aryl hydrocarbon receptor (AhR), we compared the efficacy of laquinimod in experimental autoimmune encephalomyelitis (EAE)-afflicted wild-type and AhR-deficient mice. Laquinimod failed to ameliorate clinical symptoms and leukocyte infiltration in AhR-deficient mice; however, treatment exerted neuroprotection by elevation of brain-derived neurotrophic factor (BDNF) independent of genetic profile. Thus, our data identify the AhR pathway in these mutant mice as crucial for the immunomodulatory, but not neuroprotective, efficacy of laquinimod in EAE. (C) 2016 Elsevier B.V. All rights reserved.
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页码：9 / 15
页数：7
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