Interleukin-15 regulates proliferation and self-renewal of adult neural stem cells
- PMID: 21508317
- PMCID: PMC3113763
- DOI: 10.1091/mbc.E11-01-0053
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.
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References
-
- Adunyah SE, Wheeler BJ, Cooper RS. Evidence for the involvement of LCK and MAP kinase (ERK-1) in the signal transduction mechanism of interleukin-15. Biochem Biophys Res Commun. 1997;232:754–758. - PubMed
-
- Alvarez-Buylla A, Garcia-Verdugo JM, Tramontin AD. A unified hypothesis on the lineage of neural stem cells. Nat Rev Neurosci. 2001;2:287–293. - PubMed
-
- Bauer S. Cytokine control of adult neural stem cells. Ann NY Acad Sci. 2009;1153:48–56. - PubMed
-
- Beck RD, Jr, Wasserfall C, Ha GK, Cushman JD, Huang Z, Atkinson MA, Petitto JM. Changes in hippocampal IL-15, related cytokines, and neurogenesis in IL-2 deficient mice. Brain Res. 2005;1041:223–230. - PubMed
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