血液细胞源性的白细胞介素-15(IL-15)在骨髓中支持自然杀伤细胞(NK细胞)的发育,并在骨髓中呈散在和集团化的定位。
Hematopoietic cell-derived IL-15 supports NK cell development in scattered and clustered localization within the bone marrow.
发表日期:2023 Sep 10
作者:
Shinya Abe, Takuma Asahi, Takahiro Hara, Guangwei Cui, Akihiro Shimba, Shizue Tani-Ichi, Kohei Yamada, Kazuko Miyazaki, Hitoshi Miyachi, Satsuki Kitano, Naotoshi Nakamura, Junichi Kikuta, Alexis Vandenbon, Masaki Miyazaki, Ryo Yamada, Toshiaki Ohteki, Masaru Ishii, Veronika Sexl, Takashi Nagasawa, Koichi Ikuta
来源:
Cell Reports
摘要:
自然杀伤细胞(NK细胞)是针对感染和癌症的保护性免疫应答中至关重要的先天免疫细胞。虽然NK细胞通过运用依赖于白介素15(IL-15)的方式在骨髓(BM)中分化,但IL-15的细胞来源仍然不清楚。利用NK细胞报告基因小鼠,我们展示了NK细胞以离散和聚集的方式定位于BM中。NK细胞集群与单核细胞和树突状细胞团块有重叠,而离散的NK细胞则需要CXCR4信号传导。我们通过使用特异性细胞IL-15缺陷小鼠,展示了造血细胞而非基质细胞在BM中支持NK细胞的发育通过IL-15的方式。特别地,单核细胞和树突状细胞产生的IL-15似乎对NK细胞的发育起到了贡献。这些结果表明,造血细胞是支持BM中NK细胞发育的IL-15生态位,并且BM中的NK细胞通过不同的机制以离散和聚集的方式存在,暗示了它们在免疫应答中的不同功能。版权所有© 2023 The Authors. Elsevier Inc.发行权所有。
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.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.