Interleukin-15 regulates proliferation and self-renewal of adult neural stem cells

Gomez-Nicola, Diego, Valle-Argos, Beatriz, Pallas-Bazarra, Noemí and Nieto-Sampedro, Manuel (2011) Interleukin-15 regulates proliferation and self-renewal of adult neural stem cells. Molecular Biology of the Cell, 22 (12), 1960-1970. (doi:10.1091/mbc.E11-01-0053). (PMID:21508317)

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.

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Contributors

Author: Diego Gomez-Nicola

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