Basophil-specific deletion of interleukin 15 impairs memory CD8+ T cell homeostasis in the bone marrow

Abstract

Basophils develop in the bone marrow and are associated with allergic inflammation but also contribute to protective immune responses against pathogens. Upon activation, they produce large amounts of cytokines, including interleukin (IL)-4 and IL-13. However, their physiological functions during homeostasis remain poorly defined. Here, using single-cell RNA sequencing and cytokine knock-in reporter mice, we identify basophils as the immune cell population with the highest IL-15 expression among immature and mature bone marrow leukocytes. Conditional deletion of IL-15 in basophils using Mcpt8-Cre mice results in a decrease of central-memory and CD69+ tissue-resident memory CD8+ T cells during steady-state conditions. In contrast, the homeostatic maintenance of other IL-15-dependent immune cell lineages, such as NK and NKT cells, was unaffected. Together, these findings identify basophils as a key source of IL-15 in the bone marrow that selectively supports memory CD8+ T cell maintenance.