title: IL-9 signaling affects central nervous system resident cells during inflammatory stimuli.
abstract: Interleukin (IL) 9, a dominant cytokine in Th9 cells, has been proven to play a pathogenic role in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by augmenting T cell activation and differentiation; however, whether IL-9 signaling affects central nervous system (CNS)-resident cells during CNS autoimmunity remains unknown. In the present study, we found that the IL-9 receptor (IL-9R) was highly expressed in astrocytes, oligodendrocyte progenitor cells (OPCs), oligodendrocytes and microglia cells, and that its expression was significantly upregulated in brain and spinal cord during EAE. In addition, IL-9 increased chemokine expression, including CXCL9, CCL20 and MMP3, in primary astrocytes. Although IL-9 had no effect on the proliferation of microglia cells, it decreased OPC proliferation and differentiation when in combination with other pro-inflammatory cytokines, but not with IFN-γ. IL-9 plus IFN-γ promoted OPC proliferation and differentiation. These findings indicate that CNS-restricted IL-9 signaling may be involved in the pathogenesis of MS/EAE, thus providing a potential therapeutic target for future MS/EAE treatment through disruption of CNS cell-specific IL-9 signaling.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ding
authors.affiliation: Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Cao
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China.
authors.forename: Langjun
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Bogoljub
authors.initials: B
authors.lastname: Ciric
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: a.m.rostami@jefferson.edu.
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D016906:Interleukin-9 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology; D009457:Neuroglia / Q000276:immunology*; D009836:Oligodendroglia / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D053651:Receptors, Interleukin-9 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C508448:Il9r protein, mouse; D016906:Interleukin-9; D053651:Receptors, Interleukin-9
keywords: CNS resident cells; Experimental autoimmune encephalomyelitis; IL-9; IL-9 receptor