Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan; and Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
J Immunol. 2014 Aug 15;193(4):1747-58. doi: 10.4049/jimmunol.1400868. Epub 2014 Jul 9.
NK cell development and homeostasis require IL-15 produced by both hematopoietic and parenchymal cells. Certain hematopoietic IL-15 sources, such as macrophages and dendritic cells, are known, whereas the source of parenchymal IL-15 remains elusive. Using two types of adipocyte-specific Il15(-/-) mice, we identified adipocytes as a parenchymal IL-15 source that supported NK cell development nonredundantly. Both adipocyte-specific Il15(-/-) mice showed reduced IL-15 production specifically in the adipose tissue but impaired NK cell development in the spleen and liver in addition to the adipose tissue. We also found that the adipose tissue harbored NK progenitors as other niches (e.g. spleen) for NK cell development, and that NK cells derived from transplanted adipose tissue populated the recipient's spleen and liver. These findings suggest that adipocyte IL-15 contributes to systemic NK cell development by supporting NK cell development in the adipose tissue, which serves as a source of NK cells for other organs.
自然杀伤 (NK) 细胞的发育和稳态需要由造血细胞和实质细胞产生的白细胞介素 15（IL-15）。某些造血细胞来源的 IL-15 是已知的，如巨噬细胞和树突状细胞，而实质细胞来源的 IL-15 仍然难以捉摸。使用两种类型的脂肪细胞特异性 Il15(-/-) 小鼠，我们确定脂肪细胞是一种实质细胞来源的 IL-15，它可以非冗余地支持 NK 细胞的发育。两种脂肪细胞特异性 Il15(-/-) 小鼠均表现出特异性脂肪组织中 IL-15 产生减少，但除了脂肪组织外，还会导致脾脏和肝脏中 NK 细胞发育受损。我们还发现，脂肪组织作为 NK 细胞发育的其他龛位（如脾脏）含有 NK 祖细胞，并且源自移植脂肪组织的 NK 细胞定植在受体的脾脏和肝脏中。这些发现表明，脂肪细胞 IL-15 通过支持脂肪组织中 NK 细胞的发育，从而为其他器官提供 NK 细胞来源，从而有助于系统性 NK 细胞的发育。
