In young mice, a small fraction of HSCs are IL27Ra⁺, playing an important role in myeloid recovery following a microbial insult. In old age, a TNFα-ERK-ETS1 pathway upregulation leads to increased transcription of the IL-27Ra gene, the product of which promotes myeloid bias, an inflammatory phenotype, and reduced stem cell potential. Note that some reductions in stem cell potential occur with aging on top of the IL-27Ra–mediated effects.