title: The nucleotide-binding leucine-rich repeat (NLR) family member NLRX1 mediates protection against experimental autoimmune encephalomyelitis and represses macrophage/microglia-induced inflammation.
abstract: The nucleotide binding domain and leucine-rich repeat-containing (NLR) family of proteins is known to activate innate immunity, and the inflammasome-associated NLRs are prime examples. In contrast, the concept that NLRs can inhibit innate immunity is still debated, and the impact of such inhibitory NLRs in diseases shaped by adaptive immune responses is entirely unexplored. This study demonstrates that, in contrast to other NLRs that activate immunity, NLRX1 plays a protective role in experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. When compared with wild-type controls, Nlrx1(-/-) mice have significantly worsened clinical scores and heightened CNS tissue damage during EAE. NLRX1 does not alter the production of encephalitogenic T cells in the peripheral lymphatic tissue, but Nlrx1(-/-) mice are more susceptible to adoptively transferred myelin-reactive T cells. Analysis of the macrophage and microglial populations indicates that NLRX1 reduces activation during both active and passive EAE models. This work represents the first case of an NLR that attenuates microglia inflammatory activities and protects against a neurodegenerative disease model caused by autoreactive T cells.
authors.affiliation: From the Department of Microbiology and Immunology and.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Eitas
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Chou
authors.forename: Haitao
authors.initials: H
authors.lastname: Wen
authors.forename: Denis
authors.initials: D
authors.lastname: Gris
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Robbins
authors.forename: June
authors.initials: J
authors.lastname: Brickey
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Oyama
authors.forename: Jenny P-Y
authors.initials: JP
authors.lastname: Ting
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D024101:Mitochondrial Proteins; C555655:NLRX1 protein, mouse
keywords: Cytokine; Immunology; Innate immunity; Interleukin; Neuroimmunology