# Transpresentation of interleukin 15 by stromal cell subsets regulates immune cell homeostasis

## TL;DR

This study shows that different bone marrow stromal cells use interleukin 15 to support specific immune cell populations, revealing specialized roles in immune cell maintenance.

## Contribution

The study identifies distinct stromal cell subsets responsible for IL-15 transpresentation and their specific effects on lymphocyte populations.

## Key findings

- IL-15Rα expression by BM stromal cells is essential for maintaining IL-15-dependent lymphocyte populations.
- Lepr+ and IL-7+ stromal cells regulate central memory CD8+ T cells, while Osx+ stromal cells support NKT and tissue-resident memory CD8+ T cells.
- Endothelial IL-15Rα is crucial for peripheral NK cell maturation and survival, not BM lymphocyte maintenance.

## Abstract

Stromal cells are important bone marrow (BM) niche components that regulate immune cell homeostasis through the production of cytokines such as interleukin 15 (IL-15). Although stromal-derived IL-15 is known to support lymphocyte survival, it remains unclear which stromal cell subsets are capable of IL-15 transpresentation, and how they influence specific lymphocyte populations. By using conditional IL-15 receptor alpha (IL-15Rα) deletion models, we demonstrate that IL-15Rα expression by BM stromal cells is essential for the maintenance of multiple IL-15-dependent lymphocyte populations. Deletion of IL-15Rα in Lepr+ or IL-7+ stromal cells selectively reduced central memory CD8+ T cells in the BM, whereas deletion of IL-15Rα in Osx+ stromal cells resulted in a marked loss of natural killer T (NKT) cells and tissue-resident memory CD8+ T cells. Surprisingly, endothelial-specific IL-15Rα deletion did not affect lymphocyte maintenance in the BM, but specifically impaired natural killer (NK) maturation and survival in the periphery, uncovering a role of endothelial IL-15 in mature NK cell maintenance. Together, our findings establish that transpresentation of IL-15 by distinct BM stromal cell subsets creates functionally specialized BM niches to support specific lymphocyte populations.