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.

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.

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