title: Astrocyte-targeted production of IL-10 induces changes in microglial reactivity and reduces motor neuron death after facial nerve axotomy.
abstract: Interleukin-10 (IL-10) is a cytokine that plays a crucial role in regulating the inflammatory response and immune reactions. In the central nervous system (CNS), IL-10 is mainly produced by astrocytes and microglia and it is upregulated after various insults, such as experimental autoimmune encephalomyelitis, middle cerebral artery occlusion, excitotoxicity and traumatic brain injury. To better understand the effects of IL-10 in the normal and injured CNS, we generated transgenic mice (termed GFAP-IL-10Tg) that expressed the murine IL-10 gene under the transcriptional control of the glial fibrillary acidic protein (GFAP) promoter. Previous studies demonstrated marked changes in the microglial phenotype in these mice under basal conditions. The objective of the present study was to investigate the effects of local astrocyte-targeted IL-10 production on glial activation, neuronal degeneration and leukocyte recruitment after axotomy. GFAP-IL-10Tg mice had marked changes in the phenotype of activated microglial cells, as well as in the number of microglial clusters and in microglial cell density. These microglial changes are accompanied by a twofold increase in lymphocyte infiltration in GFAP-IL-10Tg mice and around twofold decrease in neuronal cell death at 21 dpi. Altogether, our findings suggested that astrocyte-targeted production of IL-10 impacted the microglial response and lymphocyte recruitment and culminated in a beneficial effect on neuronal survival.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Institute of Neuroscience, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.
authors.forename: Nàdia
authors.initials: N
authors.lastname: Villacampa
authors.forename: Beatriz
authors.initials: B
authors.lastname: Almolda
authors.forename: Antonietta
authors.initials: A
authors.lastname: Vilella
authors.forename: Iain L
authors.initials: IL
authors.lastname: Campbell
authors.forename: Berta
authors.initials: B
authors.lastname: González
authors.forename: Bernardo
authors.initials: B
authors.lastname: Castellano
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D019771:Axotomy; D016923:Cell Death / Q000502:physiology*; D004195:Disease Models, Animal; D005154:Facial Nerve / Q000473:pathology / Q000503:physiopathology; D020220:Facial Nerve Injuries / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000473:pathology / Q000502:physiology; D008297:Male; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology*; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; C556062:IL10 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C528900:glial fibrillary astrocytic protein, mouse; D016753:Interleukin-10
keywords: CD150; CD16/32; CD18; CD39; IL-10R; MHC-II; Ym-1; arginase-1; cytokines; lymphocytes; microglia; nerve injury; neurodegeneration; neuronal survival; transgenic animal