University of Sherbrooke, Canada
Denis Gris is a head of Neuroimmunology Laboratory at the University of Sherbrooke QC Canada. He graduated from University of Western Ontario from Dr. Weaver’s laboratory where he studied inflammation after spinal cord injury. He moved to pursue his postdoctoral studies with Dr. Ting at university of North Carolina at Chapel Hills NC USA where he began to investigate role of NLRs in neurodegeneration. His main interest is to discover novel anti-inflammatory pathways within the central nervous system and use this knowledge to design therapies for neurological diseases including multiple sclerosis amyotrophic lateral sclerosis autism and epilepsy.
Although detrimental role of the adaptive immune system has long been established, the cause of multiple sclerosis (MS) remains unknown. Every person has a complement of autoreactive lymphocytes and everybody experience episodes of an infection when these lymphocytes enter central nervous system, but only relatively small fraction of people develop MS. It is postulated that the existing inhibitory pathways keep in check local tissue inflammation that provokes the excessiveorgan-specific immune response. Recently discovered family of proteins called nucleotide–binding leucine-rich-repeat-containing proteins (NLRs)are good candidates to fulfill such purpose. They may activate or inhibit major proinflammatory pathways regulatingthe innate and adaptive immune responses. Using experimental autoimmune encephalomyelitis model in KO mice, other’s and present studies show that NLRs including (NOD1, NOD2, and Nlrp3) may promote development of MS. Dissecting inhibitory pathways thatmay play role in stopping the disease,we showed that Nlrx1 and Nlrp12 inhibit progression of EAE in mice. It was noticed that the pathophysiology of the disease was affected at multiple levels including neurons, glial cells as well as peripheral immune system. It was found that Nlrx1 plays protective role in neuronal population. Also, it reduces reactive astrogliosis. Nlrp12 on the other hand regulates activation of microglial response and affects peripheral innate immune responses. Taking together these studies demonstrate crucial role of NLRs in regulating the tissue homeostasis and local inflammation during MS.
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