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

The adult subventricular zone (SVZ) is the main neurogenic niche in normal adult brain of mice and rats. The adult SVZ contains neural stem cells (NSCs) that mainly differentiate into committed neuroblasts. The new generated neuroblasts accumulate in dorsal SVZ where they further differentiate and initiate a long migration pathway to their final destination the olfactory bulb (OB). In here we report a new role for Interleukin 10 (IL-10) different from its well known anti-inflammatory properties. We reveal that IL-10 receptor is expressed in Nestin+ progenitors restricted to the dorsal SVZ in adult brain. Through IL-10 gain models we observed that IL-10 maintains neural progenitors in an undifferentiated stage by keeping progenitors in active cycle and up-regulating the presence of pro-neural genes markers (Nestin, Sox genes, Musashi, Mash1) in detriment of neuronal gene expression (Numb, DCX, TUBB3). On top, IL-10 reduces neuronal differentiation and finally impairs endogenous neurogenesis. Consistently, in the absence of IL-10 in vivo neuronal differentiation among 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 adult neurogenesis in adult normal brain.