The ageing immune system is characterized by weaker adaptive immune responses and increased inflammatory pathology. Here, Ross et al. show that antibody-mediated depletion of myeloid-biased haematopoietic stem cells (HSCs) can protect against such age-associated dysfunction.

HSCs can be broadly divided into two subsets: balanced HSCs, which lead to equal production of lymphoid and myeloid cells; and myeloid HSCs, which mainly give rise to myeloid cells. The ratio of myeloid to balanced HSCs increases with age, and this is thought to contribute to immune dysfunction. The authors set out to define surface antigens that can be used to target myeloid HSCs. By screening transcriptional datasets of HSCs, they found 12 candidate genes, with antibody-staining analyses identifying CD150, CD41, CD62p and NEO1 as candidate antigens for selectively targeting myeloid HSCs.