title: Interleukin-15 regulates proliferation and self-renewal of adult neural stem cells.
abstract: The impact of inflammation is crucial for the regulation of the biology of neural stem cells (NSCs). Interleukin-15 (IL-15) appears as a likely candidate for regulating neurogenesis, based on its well-known mitogenic properties. We show here that NSCs of the subventricular zone (SVZ) express IL-15, which regulates NSC proliferation, as evidenced by the study of IL-15-/- mice and the effects of acute IL-15 administration, coupled to 5-bromo-2'-deoxyuridine/5-ethynyl-2'-deoxyuridine dual-pulse labeling. Moreover, IL-15 regulates NSC differentiation, its deficiency leading to an impaired generation of neuroblasts in the SVZ-rostral migratory stream axis, recoverable through the action of exogenous IL-15. IL-15 expressed in cultured NSCs is linked to self-renewal, proliferation, and differentiation. IL-15-/- NSCs presented deficient proliferation and self-renewal, as evidenced in proliferation and colony-forming assays and the analysis of cell cycle-regulatory proteins. Moreover, IL-15-deficient NSCs were more prone to differentiate than wild-type NSCs, not affecting the cell population balance. Lack of IL-15 led to a defective activation of the JAK/STAT and ERK pathways, key for the regulation of proliferation and differentiation of NSCs. The results show that IL-15 is a key regulator of neurogenesis in the adult and is essential to understanding diseases with an inflammatory component.
authors.affiliation: Functional and Systems Neurobiology Department, Cajal Institute (CSIC), Madrid, Spain. dgomeznicola@gmail.com
authors.forename: Diego
authors.initials: D
authors.lastname: Gómez-Nicola
authors.forename: Beatriz
authors.initials: B
authors.lastname: Valle-Argos
authors.forename: Noemí
authors.initials: N
authors.lastname: Pallas-Bazarra
authors.forename: Manuel
authors.initials: M
authors.lastname: Nieto-Sampedro
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000032:analysis; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D050791:STAT Transcription Factors / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D019409:Interleukin-15; D009419:Nerve Tissue Proteins; D050791:STAT Transcription Factors; D053612:Janus Kinases; D048049:Extracellular Signal-Regulated MAP Kinases