Interleukin-10 regulates progenitor differentiation and modulates neurogenesis in adult brain

Abstract

The adult subventricular zone (SVZ) is the main neurogenic niche in the adult brain of mice and rats. The adult SVZ contains neural stem cells (NSCs) that primarily differentiate into committed neuroblasts. The newly generated neuroblasts accumulate in dorsal SVZ where they further differentiate and initiate a long migration pathway to their final destination, the olfactory bulb (OB). Here, we report a new role for Interleukin 10 (IL-10) that is different to its well-known anti-inflammatory properties. We show that the IL-10 receptor is expressed in Nestin-positive progenitors restricted to the dorsal SVZ in adult brain. Using IL-10 gain models, we observed that IL-10 maintains neural progenitors in an undifferentiated state by keeping progenitors in an active cycle where pro-neural gene markers (Nestin, Sox1, Sox2, Musashi, Mash1) are upregulated and neuronal gene expression (Numb, DCX, TUBB3) is downregulated. In addition, IL-10 reduces neuronal differentiation and ultimately impairs endogenous neurogenesis. Consistently, in the absence of IL-10, in vivo neuronal differentiation of SVZ progenitors is enhanced and the incorporation of new neurons in the adult OB is increased. Thus, our results provide the first evidence that IL-10 acts as a growth factor on SVZ progenitors and regulates neurogenesis in normal adult brain.