o:2506 Hematopoietic cell-derived IL-15 supports NK cell development in scattered and clustered localization within the bone marrow en Natural killer (NK) cells are innate immune cells critical for protective immune responses against infection and cancer. Although NK cells differentiate in the bone marrow (BM) in an interleukin-15 (IL-15)-dependent manner, the cellular source of IL-15 remains elusive. Using NK cell reporter mice, we show that NK cells are localized in the BM in scattered and clustered manners. NK cell clusters overlap with monocyte and dendritic cell accumulations, whereas scattered NK cells require CXCR4 signaling. Using cell-specific IL-15-deficient mice, we show that hematopoietic cells, but not stromal cells, support NK cell development in the BM through IL-15. In particular, IL-15 produced by monocytes and dendritic cells appears to contribute to NK cell development. These results demonstrate that hematopoietic cells are the IL-15 niche for NK cell development in the BM and that BM NK cells are present in scattered and clustered compartments by different mechanisms, suggesting their distinct functions in the immune response. Mice; Animals; Bone Marrow; Interleukin-15; Bone Marrow Cells; Cell Differentiation; Killer Cells, Natural 1552099 10.1016/j.celrep.2023.113127 2024-02-09T09:04:15.358Z 44 yes 46 Shinya Abe Kyoto University Takuma Asahi Kyoto University person Takahiro Hara Kyoto University person Guangwei Cui Kyoto University person Akihiro Shimba Kyoto University person Shizue Tani-Ichi Kyoto University person Kohei Yamada Kyoto University person Kazuko Miyazaki Kyoto University person Hitoshi Miyachi Kyoto University person Satsuki Kitano Kyoto University person Naotoshi Nakamura Nagoya University person Junichi Kikuta Osaka University person Alexis Vandenbon Kyoto University person Masaki Miyazaki Kyoto University person Ryo Yamada Kyoto University person Toshiaki Ohteki Tokyo Medical and Dental University person Masaru Ishii Osaka University person Veronika Sexl University of Veterinary Medicine Vienna person 0000-0001-9363-0412 Takashi Nagasawa Osaka University person Koichi Ikuta Kyoto University person application/pdf 9159637 https://phaidra.vetmeduni.ac.at/o:2506 no yes 16 70 1552253 Cell Reports 24 42 9 Cell Press 2023