The leukotriene B4 receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis

Leukotriene B-4 (LTB4) 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 LTB4. 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 (C) 2010 Elsevier Inc All rights reserved