title: MicroRNA223 promotes pathogenic T-cell development and autoimmune inflammation in central nervous system in mice.
abstract: Multiple sclerosis (MS) is an incurable central nervous system autoimmune disease. Understanding MS pathogenesis is essential for the development of new MS therapies. In the present study, we identified a novel microRNA (miR) that regulates experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Expression of miR223 was up-regulated specifically in spinal cords and lymphoid organs but not in other examined tissues. A global miR223 knockout (miR223(-/-) ) in mice led to a significant delay in EAE onset, reduction in spinal cord lesion, and lessening of neurological symptoms. These protective effects could be reproduced in bone marrow chimeras reconstituted with miR223(-/-) haematopoietic stem cells. We also found that miR223 deficiency reduced T helper type 1 (Th1) and Th17 infiltration into spinal cords. To address underlying mechanisms, we investigated the role of miR223 in regulating the function, development and interaction of the major immune cells. Expression of the genes associated with dendritic cell (DC) activation (CD86 and MHC II) and Th1 and Th17 differentiation [interleukin-12 (IL-12) and IL-23, respectively] was significantly decreased in the spleens of miR223(-/-) mice bearing EAE. The miR223(-/-) DCs expressed significantly lower levels of basal and lipopolysaccharide-induced IL-12 and IL-23 compared with the wild-type DCs. These data are consistent with the observed lower efficiency of miR223(-/-) DCs to support Th1 and Th17 differentiation from naive T cells over-expressing an EAE antigen-specific T-cell receptor. Our data suggest that miR223 promotes EAE, probably through enhancing DC activation and subsequently the differentiation of naive T cells toward Th1 and Th17 effector cells.
authors.affiliation: J.L. Pettis VA Medical Center, Loma Linda, CA, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Satoorian
authors.affiliation: Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Tang
authors.affiliation: J.L. Pettis VA Medical Center, Loma Linda, CA, USA.|Department of Ultrasound & Imaging, Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Jidong
authors.initials: J
authors.lastname: Xiao
authors.affiliation: J.L. Pettis VA Medical Center, Loma Linda, CA, USA.|Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Weirong
authors.initials: W
authors.lastname: Xing
authors.affiliation: Department of Pharmacological Sciences, School of Pharmacy, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Weixing
authors.initials: W
authors.lastname: Shi
authors.affiliation: J.L. Pettis VA Medical Center, Loma Linda, CA, USA.|Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Kin-Hing William
authors.initials: KH
authors.lastname: Lau
authors.affiliation: Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Baylink
authors.affiliation: J.L. Pettis VA Medical Center, Loma Linda, CA, USA.|Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Qin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D013116:Spinal Cord / Q000473:pathology / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D053759:Interleukin-23; C544877:MIRN223 microRNA, mouse; D035683:MicroRNAs; D018664:Interleukin-12
keywords: T cells; autoinflammatory disease; experimental autoimmune encephalomyelitis/multiple sclerosis; neuroimmunology