The leukotriene B4 receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis.
Leukotriene B(4) (LTB(4)) is a potent chemoattractant and activator of neutrophils, macrophages and T cells. These cells are a key component of inflammation and all express BLT1, a high affinity G-protein-coupled receptor for LTB(4). However, little is known about the neuroimmune functions of BLT1. In this study, we describe a distinct role for BLT1 in the pathology of experimental autoimmune encephalomyelitis (EAE) and T(H)1/T(H)17 immune responses. BLT1 mRNA was highly upregulated in the spinal cord of EAE mice, especially during the induction phase. BLT1(-/-) mice had delayed onset and less severe symptoms of EAE than BLT1(+/+) mice. Additionally, inflammatory cells were recruited to the spinal cord of asymptomatic BLT1(+/+), but not BLT1(-/-) mice before the onset of disease. Ex vivo studies showed that both the proliferation and the production of IFN-gamma, TNF-alpha, IL-17 and IL-6 were impaired in BLT1(-/-) cells, as compared with BLT1(+/+) cells. Thus, we suggest that BLT1 exacerbates EAE by regulating the migration of inflammatory cells and T(H)1/T(H)17 immune responses. Our findings provide a novel therapeutic option for the treatment of multiple sclerosis and other T(H)17-mediated diseases.
Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. kihara-yasuyuki@umin.net
Yasuyuki
Y
Kihara
Takehiko
T
Yokomizo
Akiko
A
Kunita
Yasuyuki
Y
Morishita
Masashi
M
Fukayama
Satoshi
S
Ishii
Takao
T
Shimizu
D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018102:Receptors, Leukotriene B4 / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4