Expression of the G-protein coupled receptor EBI2 in T cells is highly regulated and confers pathogenicity to myelin specific Th17 cells

The role of NFkappaB inducing kinase (NIK) in the pathogenicity of EAE

pathways (PTPN6, SLC3A2, VAV3, DDR1) and modulators of oxidative stress (MT1A, HMOX1, SLC30A1) were also significantly affected by the CBD treatment. The microarray results were confirmed using qPCR on selected gene targets. Immunoblotting demonstrated that CBD reduces IL-17 by decreasing STAT3 phosphorylation and increasing that of STAT5. In conclusion, our observations increase our understanding of the mechanisms of the anti-inflammatory activities of CBD.

The role of NG2 and OPC in induction and development of CNS inflammation

encephalitis (EAE) mouse models (J Neurosci 31:669, 2011; Brain 136:1760, 2013). Further, it has been shown that in addition to infiltrating leukocytes, astrocytes and microglia also exhibit high expression of EMMPRIN in diseased brain. EMMPRIN has been reported to interact with monocarboxylate transporter-1 (MCT-1) in astrocytes; the lattermediates lactate transport to neurons. Given that perturbation in energymetabolism can have catastrophic effects on homeostasis of the brain, it is paramount to understand EMMPRIN expression in astrocytes in normal andMS brain.We have used human fetal astrocytes (HFA) and determined their EMMPRIN levels by flow cytometry and microscopy. We found that HFA…

NF-κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling

NF-κB inducing kinase (NIK) is the key protein of the non-canonical NF-κB pathway and is important for the development of lymph nodes and other secondary immune organs. We elucidated the specific role of NIK in T cells using T-cell specific NIK-deficient (NIKΔT) mice. Despite showing normal development of lymphoid organs, NIKΔT mice were resistant to induction of CNS autoimmunity. T cells from NIKΔT mice were deficient in late priming, failed to up-regulate T-bet and to transmigrate into the CNS. Proteomic analysis of activated NIK-/- T cells showed de-regulated expression of proteins involved in the formation of the immunological synapse: in particular, proteins involved in cytoskeleton dy…

EBI2 Is Highly Expressed in Multiple Sclerosis Lesions and Promotes Early CNS Migration of Encephalitogenic CD4 T Cells

Arrival of encephalitogenic T cells at inflammatory foci represents a critical step in development of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. EBI2 and its ligand, 7{alpha},25-OHC, direct immune cell localization in secondary lymphoid organs. CH25H and CYP7B1 hydroxylate cholesterol to 7{alpha},25-OHC. During EAE, we found increased expression of CH25H by microglia and CYP7B1 by CNS-infiltrating immune cells elevating the ligand concentration in the CNS. Two critical pro-inflammatory cytokines, interleukin-23 (IL-23) and interleukin-1 beta (IL-1{beta}), maintained expression of EBI2 in differentiating Th17 cells. In line with this, EBI2 enhan…