Person: Elyaman, Wassim
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Elyaman
First Name
Wassim
Name
Elyaman, Wassim
5 results
Search Results
Now showing 1 - 5 of 5
Publication Innate and adaptive immunity in human epilepsies(John Wiley and Sons Inc., 2017) Bauer, Jan; Becker, Albert J.; Elyaman, Wassim; Peltola, Jukka; Rüegg, Stephan; Titulaer, Maarten J.; Varley, James A.; Beghi, EttoreSummary Inflammatory mechanisms have been increasingly implicated in the origin of seizures and epilepsy. These mechanisms are involved in the genesis of encephalitides in which seizures are a common complaint. Experimental and clinical evidence suggests different inflammatory responses in the brains of patients with epilepsy depending on the etiology. In general, activation of both innate and adaptive immunity plays a role in refractory forms of epilepsy. Epilepsies in which seizures develop after infiltration of cells of the adaptive immune system in the central nervous system (CNS) include a broad range of epileptic disorders with different (known or unknown) etiologies. Infiltration of lymphocytes is observed in autoimmune epilepsies, especially the classical paraneoplastic encephalitides with antibodies against intracellular tumor antigens. The presence of lymphocytes in the CNS also has been found in focal cerebral dysplasia type 2 and in cortical tubers. Various autoantibodies have been shown to be associated with temporal lobe epilepsy (TLE) and hippocampal sclerosis of unknown etiology, which may be due to the presence of viral DNA. During the last decade, an increasing number of antineuronal autoantibodies directed against membranous epitopes have been discovered and are associated with various neurologic syndromes, including limbic encephalitis. A major challenge in epilepsy is to define biomarkers, which would allow the recognition of patient populations who might benefit from immune‐modulatory therapies. Some peripheral inflammatory markers appear to be differentially expressed in patients with medically controlled and medically refractory and, as such, could be used for diagnostic, prognostic, or therapeutic purposes. Establishing an autoimmune basis in patients with drug‐resistant epilepsy allows for efficacious and targeted immunotherapy. Although current immunotherapies can give great benefit to the correctly identified patient, there are limitations to their efficacy and they may have considerable side effects. Thus the identification of new immunomodulatory compounds remains of utmost importance.Publication MS AHI1 genetic risk promotes IFNγ+ CD4+ T cells(Lippincott Williams & Wilkins, 2017) Kaskow, Belinda; Buttrick, Thomas S.; Klein, Hans-Ulrich; White, Charles; Bourgeois, Justin R.; Ferland, Russell J.; Patsopoulos, Nikolaos; Bradshaw, Elizabeth M.; De Jager, Philip; Elyaman, WassimObjective: To study the influence of the Abelson helper integration site 1 (AHI1) locus associated with MS susceptibility on CD4+ T cell function. Methods: We characterized the chromatin state of T cells in the MS-associated AHI1 linkage disequilibrium (LD) block. The expression and the role of the AHI1 variant were examined in T cells from genotyped healthy subjects who were recruited from the PhenoGenetic Project, and the function of AHI1 was explored using T cells from Ahi1 knockout mice. Results: Chromatin state analysis reveals that the LD block containing rs4896153, which is robustly associated with MS susceptibility (odds ratio 1.15, p = 1.65 × 10−13), overlaps with strong enhancer regions that are present in human naive and memory CD4+ T cells. Relative to the rs4896153A protective allele, the rs4896153T susceptibility allele is associated with decreased AHI1 mRNA expression, specifically in naive CD4+ T cells (p = 1.73 × 10−74, n = 213), and we replicate this effect in an independent set of subjects (p = 2.5 × 10−9, n = 32). Functional studies then showed that the rs4896153T risk variant and the subsequent decreased AHI1 expression were associated with reduced CD4+ T cell proliferation and a specific differentiation into interferon gamma (IFNγ)–positive T cells when compared with the protective rs4896153A allele. This T cell phenotype was also observed in murine CD4+ T cells with genetic deletion of Ahi1. Conclusions: Our findings suggest that the effect of the AHI1 genetic risk for MS is mediated, in part, by enhancing the development of proinflammatory IFNγ+ T cells that have previously been implicated in MS and its mouse models.Publication Notch Signaling and T-Helper Cells in EAE/MS(Hindawi Publishing Corporation, 2013) Bassil, Ribal; Orent, Will; Elyaman, WassimThe Notch signaling pathway preservation across species hints to the indispensable role it plays during evolution. Over the last decade the science community has extensively studied the Notch signaling pathway, with Notch emerging as a key player in embryogenesis, tissue homeostasis, angiogenesis, and immunoregulation. Multiple sclerosis (MS) is an incurable yet treatable autoimmune chronic inflammatory disease of the central nervous system. The aim of this review is to provide a brief description of the Notch signaling pathway, and summarize the current literature implicating Notch in the pathogenesis of MS.Publication AKAP9 regulates activation-induced retention of T lymphocytes at sites of inflammation(Nature Publishing Group, 2015) Herter, Jan M.; Grabie, Nir; Cullere, Xavier; Azcutia, Veronica; Rosetti, Florencia; Bennett, Paul; Herter-Sprie, Grit S.; Elyaman, Wassim; Luscinskas, Francis; Lichtman, Andrew; Mayadas, TanyaThe mechanisms driving T cell homing to lymph nodes and migration to tissue are well described but little is known about factors that affect T cell egress from tissues. Here, we generate mice with a T cell-specific deletion of the scaffold protein A kinase anchoring protein 9 (AKAP9) and use models of inflammatory disease to demonstrate that AKAP9 is dispensable for T cell priming and migration into tissues and lymph nodes, but is required for T cell retention in tissues. AKAP9 deficiency results in increased T cell egress to draining lymph nodes, which is associated with impaired T cell re-activation in tissues and protection from organ damage. AKAP9-deficient T cells exhibit reduced microtubule-dependent recycling of TCRs back to the cell surface and this affects antigen-dependent activation, primarily by non-classical antigen-presenting cells. Thus, AKAP9-dependent TCR trafficking drives efficient T cell re-activation and extends their retention at sites of inflammation with implications for disease pathogenesis.Publication Tiam1/Rac1 complex controls Il17a transcription and autoimmunity(Nature Publishing Group, 2016) Kurdi, Ahmed T.; Bassil, Ribal; Olah, Marta; Wu, Chuan; Xiao, Sheng; Taga, Mariko; Frangieh, Michael; Buttrick, Thomas; Orent, Will; Bradshaw, Elizabeth M.; Khoury, Samia; Elyaman, WassimRORγt is a master transcription factor of Th17 cells and considered as a promising drug target for the treatment of autoimmune diseases. Here, we show the guanine nucleotide exchange factor, Tiam1, and its cognate Rho-family G protein, Rac1, regulate interleukin (IL)17A transcription and autoimmunity. Whereas Tiam1 genetic deficiency weakens IL-17A expression partially and inhibits the development of experimental autoimmune encephalomyelitis (EAE), deletion of Rac1 in T cells exhibits more robust effects on Th17 cells and EAE. We demonstrate Tiam1 and Rac1 form a complex with RORγt in the nuclear compartment of Th17 cells, and together bind and activate the Il17 promoter. The clinical relevance of these findings is emphasized by pharmacological targeting of Rac1 that suppresses both murine and human Th17 cells as well as EAE. Thus, our findings highlight a regulatory pathway of Tiam1/Rac1 in Th17 cells and suggest that it may be a therapeutic target in multiple sclerosis.