https://phaidra.vetmeduni.ac.at/o:2506 Hematopoietic cell-derived IL-15 supports NK cell development in scattered and clustered localization within the bone marrow Abe, Shinya Shinya Abe Kyoto University Ikuta, Koichi Koichi Ikuta Kyoto University Nagasawa, Takashi Takashi Nagasawa Osaka University Sexl, Veronika Veronika Sexl 0000-0001-9363-0412 University of Veterinary Medicine Vienna Ishii, Masaru Masaru Ishii Osaka University Ohteki, Toshiaki Toshiaki Ohteki Tokyo Medical and Dental University Yamada, Ryo Ryo Yamada Kyoto University Miyazaki, Masaki Masaki Miyazaki Kyoto University Vandenbon, Alexis Alexis Vandenbon Kyoto University Kikuta, Junichi Junichi Kikuta Osaka University Nakamura, Naotoshi Naotoshi Nakamura Nagoya University Kitano, Satsuki Satsuki Kitano Kyoto University Miyachi, Hitoshi Hitoshi Miyachi Kyoto University Miyazaki, Kazuko Kazuko Miyazaki Kyoto University Yamada, Kohei Kohei Yamada Kyoto University Tani-Ichi, Shizue Shizue Tani-Ichi Kyoto University Shimba, Akihiro Akihiro Shimba Kyoto University Cui, Guangwei Guangwei Cui Kyoto University Asahi, Takuma Takuma Asahi Kyoto University Hara, Takahiro Takahiro Hara Kyoto University Cell Press text eng 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 http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:2506/download 10.1016/j.celrep.2023.113127 https://phaidra.vetmeduni.ac.at/o:605 application/pdf Cell Reports 42(9) (2023) Cell Reports 42 9 8.74 MB 2023