title: CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation.
abstract: Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Seong Bum
authors.initials: SB
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Erdenebelig
authors.initials: E
authors.lastname: Uyangaa
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Ajit Mahadev
authors.initials: AM
authors.lastname: Patil
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Han
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.|Department of Bioactive Material Sciences, Graduate School, Chonbuk National University, Jeonju 54896, Republic of Korea.
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.|Department of Bioactive Material Sciences, Graduate School, Chonbuk National University, Jeonju 54896, Republic of Korea.
authors.forename: John Hwa
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Pusan National University, School of Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Koanhoi
authors.initials: K
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.|Department of Bioactive Material Sciences, Graduate School, Chonbuk National University, Jeonju 54896, Republic of Korea.
authors.forename: Seong Kug
authors.initials: SK
authors.lastname: Eo
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology*; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D018349:Encephalitis Viruses, Japanese; D004671:Encephalitis, Arbovirus / Q000235:genetics / Q000276:immunology*; D018177:Flavivirus Infections / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D000950:Antigens, Ly; D039521:CD11c Antigen; C494192:Ly-6C antigen, mouse