(Vienna, 09 July 2025) A research team at the Medical University of Vienna led by Dietmar Herndler-Brandstetter has investigated how bone marrow niches orchestrate immune cell development and promote long-term survival and function of mature immune cells. The study reveals that stromal cell subtypes have a different capacity to produce the survival cytokine interleukin 15 (IL-15) and thereby differently regulate the development and survival of immune cells. The results have been published in the Journal “Nature Communications”.
Mesenchymal stromal cells are a heterogeneous cell population that includes mesenchymal stem cells, fibroblasts, osteo-lineage stromal cells, pericytes and endothelial cells. Their potential is being investigated in the field of regenerative medicine and cancer as well as in the treatment of autoimmune diseases, due to their immunosuppressive activity. However, mesenchymal stromal cells can also promote immune cell function and survival. They play a crucial role in the bone marrow by forming microenvironmental niches that support the survival of hematopoietic stem cells and orchestrate the development and long-term maintenance of immune cells.
Using a novel fluorescent reporter mouse model that was generated in collaboration with Richard A. Flavell (Yale University, USA), the researchers were able to generate a map of IL-15-producing stromal cell subtypes in the bone marrow. Single cell transcriptomic profiling and multicolor flow cytometry revealed heterogeneity among stromal cell subtypes to produce IL-15. Conditional deletion of IL-15 in osteo-lineage stromal cells impaired the development of natural killer cells and decreased the survival of cytotoxic memory CD8 T cells in the bone marrow. Deletion of IL-15 in endothelial cells reduced the survival of natural killer cells and memory CD8 T cells in the blood but not in the bone marrow.
"Our results show a functional specialization of stromal cells in the bone marrow and how this regulates the early steps of natural killer cell development and the long-term survival of cytotoxic memory T cells" says first author Carmen Stecher from the Center for Cancer Research at MedUni Vienna.
The results highlight the remarkable ability of stromal cells to shape immune cell function. The communication between stromal and immune cells also plays a key role in cancer. The new insights into stromal cell subtypes may pave the way for the development of novel immunomodulatory therapies.
This research was supported by the Austrian Science Fund (FWF), the Austrian Academy of Sciences (ÖAW) and the Vienna Science and Technology Fund (WWTF).
Publication: Nature Communications
Heterogeneity of IL-15-expressing mesenchymal stromal cells controls natural killer cell development and immune cell homeostasis.
Carmen Stecher, Romana Bischl, Anna Schmid-Böse, Stefanie Ferstl, Elisabeth Potzmann, Magdalena Frank, Nina Braun, Matthias Farlik, Richard A Flavell, Dietmar Herndler-Brandstette.r
DOI: 10.1038/s41467-025-61231-0
https://www.nature.com/articles/s41467-025-61231-0