title: Deficiency of IκB Kinase β in Myeloid Cells Reduces Severity of Experimental Autoimmune Encephalomyelitis.
abstract: In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), peripherally developed myelin-reactive T lymphocytes stimulate myeloid cells (ie, microglia and infiltrated macrophages) to trigger an inflammatory reaction in the central nervous system, resulting in demyelination and neurodegeneration. IκB kinase β (IKKβ) is a kinase that modulates transcription of inflammatory genes. To investigate the pathogenic role of IKKβ in MS, we developed strains in which IKKβ was conditionally ablated in myeloid cells and established active or passive EAE in these animals. Deficiency of IKKβ in myeloid cells ameliorated EAE symptoms and suppressed neuroinflammation, as shown by decreased infiltration of T lymphocytes and macrophages and reduced inflammatory gene transcription in the spinal cord at the peak or end stage of EAE. Myeloid deficiency of IKKβ also reduced the transcription of Rorc or Il17 genes in T lymphocytes isolated from lymph nodes, spleen, and spinal cord of EAE mice. Moreover, cultured splenocytes isolated from myeloid IKKβ-deficient EAE mice released less IL-17, interferon-γ, and granulocyte-macrophage colony-stimulating factor after treatment with myelin peptide than splenocytes from IKKβ wild-type EAE mice. Thus, deficiency of myeloid IKKβ attenuates the severity of EAE by inhibiting both the neuroinflammatory activity and the activation of encephalitogenic T lymphocytes. These results suggest IKKβ may be a potential target for MS patients, especially when neuroinflammation is the primary problem.
authors.affiliation: Department of Neurology, University of the Saarland, Homburg/Saar, Germany.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Hao
authors.affiliation: Department of Neurology, University of the Saarland, Homburg/Saar, Germany.
authors.forename: Yann
authors.initials: Y
authors.lastname: Decker
authors.affiliation: Department of Neurology, University of the Saarland, Homburg/Saar, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Schnöder
authors.affiliation: Department of Neurology, University of the Saarland, Homburg/Saar, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schottek
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji University Medical School, Shanghai, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute for Clinical and Experimental Surgery, University of the Saarland, Homburg/Saar, Germany.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.affiliation: Department of Neurology, University of the Saarland, Homburg/Saar, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Fassbender
authors.affiliation: Department of Neurology, University of the Saarland, Homburg/Saar, Germany; Department of Clinical Laboratory, Tongji Hospital, Tongji University Medical School, Shanghai, People's Republic of China. Electronic address: a.liu@mx.uni-saarland.de.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology* / Q000235:genetics; D015321:Gene Rearrangement; D051550:I-kappa B Kinase / Q000172:deficiency* / Q000235:genetics; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D017628:Microglia / Q000201:enzymology; D022423:Myeloid Cells / Q000201:enzymology*; D013116:Spinal Cord / Q000201:enzymology; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D051550:I-kappa B Kinase