title: IKKβ-mediated inflammatory myeloid cell activation exacerbates experimental autoimmune encephalomyelitis by potentiating Th1/Th17 cell activation and compromising blood brain barrier.
abstract: The inflammatory myeloid cell activation is one of the hallmarks of experimental autoimmune encephalomyelitis (EAE), yet the in vivo role of the inflammatory myeloid cell activation in EAE has not been clearly resolved. It is well-known that IKK/NF-κB is a key signaling pathway that regulates inflammatory myeloid activation.
  
  
  
  We investigated the in vivo role of inflammatory myeloid cell activation in myelin oligodendrocyte glycoprotein (MOG) peptides-induced EAE using myeloid cell type-specific ikkβ gene conditional knockout-mice (LysM-Cre/Ikkβ (F/F) ).
  
  
  
  In our study, LysM-Cre/Ikkβ (F/F) mice had alleviated clinical signs of EAE corresponding to the decreased spinal demyelination, microglial activation, and immune cell infiltration in the spinal cord, compared to the wild-type mice (WT, Ikkβ (F/F) ). Myeloid ikkβ gene deletion significantly reduced the percentage of CD4(+)/IFN-γ(+) (Th1) and CD4(+)/IL-17(+) (Th17) cells but increased the percentages of CD4(+)/CD25(+)/Foxp3(+) (Treg) cells in the spinal cord and lymph nodes, corresponding to the altered mRNA expression of IFN-γ, IL-17, IL-23, and Foxp3 in the spinal cords of LysM-Cre/Ikkβ (F/F) EAE mice. Also, the beneficial effect of myeloid IKKβ deletion in EAE corresponded to the decreased permeability of the blood brain barrier (BBB).
  
  
  
  Our findings strongly suggest that IKK/NF-kB-induced myeloid cell activation exacerbates EAE by activating Th1 and Th17 responses and compromising the BBB. The development of NF-κB inhibitory agents with high efficacy through specific targeting of IKKβ in myeloid cells might be of therapeutic potential in MS and other autoimmune disorders.
authors.affiliation: Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.|Brain Korea 21 Plus Program, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Veterinary Medicine, Jeju National University, Jeju, 63243, Republic of Korea.
authors.forename: So Jin
authors.initials: SJ
authors.lastname: Bing
authors.affiliation: Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.|Brain Korea 21 Plus Program, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Jonghee
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Minhee
authors.initials: M
authors.lastname: Jang
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Gihyun
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Neuroscience and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 08826, Republic of Korea.
authors.forename: Hyunkyoung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Cosmetology, Hanseo University, Seosan, 31962, Republic of Korea.
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Chang
authors.affiliation: Department of Veterinary Medicine, Jeju National University, Jeju, 63243, Republic of Korea.
authors.forename: Youngheun
authors.initials: Y
authors.lastname: Jee
authors.affiliation: Department of Neuroscience and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 08826, Republic of Korea. sjlee87@snu.ac.kr.
authors.forename: Sung Joong
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea. ihcho@khu.ac.kr.|Brain Korea 21 Plus Program, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea. ihcho@khu.ac.kr.|Institute of Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea. ihcho@khu.ac.kr.
authors.forename: Ik-Hyun
authors.initials: IH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D051550:I-kappa B Kinase / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D008213:Lymphocyte Activation; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D051550:I-kappa B Kinase
keywords: Blood brain barrier; Experimental autoimmune encephalomyelitis; IKKβ conditional deletion; Myeloid cell; T cell