title: Brain interleukin-15 in neuroinflammation and behavior.
abstract: Interleukin (IL)-15 is a ubiquitously expressed cytokine existing in both intracellular and secretory forms. Here we review the expression, regulation, and functions of IL15 and its receptors in the brain. IL15 receptors show robust upregulation after neuroinflammation, suggesting a major role of IL15 signaling in cerebral function. Involvement of the IL15 system in neuropsychiatric behavior is reflected by the effects of IL15, IL15Rα, and IL2Rγ deletions on neurobehavior and neurotransmitters, the effects of IL15 treatment on neuronal activity, and the potential role of IL15 in neuroplasticity/neurogenesis. The results show that IL15 modulates GABA and serotonin transmission. This may underlie deficits in mood (depressive-like behavior and decreased normal anxiety) and memory, as well as activity level, sleep, and thermoregulation. Although IL15 has only a low level of permeation across the blood-brain barrier, peripheral IL15 is able to activate multiple signaling pathways in neurons widely distributed in CNS regions. The effects of IL15 in "preventing" neuropsychiatric symptoms in normal mice implicate a potential therapeutic role of this polypeptide cytokine.
authors.affiliation: Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. weihong.pan@pbrc.edu
authors.forename: Weihong
authors.initials: W
authors.lastname: Pan
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.forename: Hung
authors.initials: H
authors.lastname: Hsuchou
authors.forename: Eagle Yi-Kung
authors.initials: EY
authors.lastname: Huang
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Mishra
authors.forename: Abba J
authors.initials: AJ
authors.lastname: Kastin
mesh_terms: D000339:Affect / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D019409:Interleukin-15 / Q000378:metabolism / Q000502:physiology*; D053720:Interleukin-15 Receptor alpha Subunit / Q000378:metabolism / Q000502:physiology; D008568:Memory / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation
chemical_list: D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D014409:Tumor Necrosis Factor-alpha