Cytokine-Based Generation of CD49a+Eomes−/+ Natural Killer Cell Subsets

Recent studies have identified CD49a+Eomes− and CD49a+Eomes+ subsets of tissue-resident NK (trNK) cells in different organs of the mouse. However, the characteristics of CD49a+Eomes−/+ NK cell development and the regulation of Eomes expression in NK cells remain unclear. Here, we established an in vitro cytokine-based feeder-free system in which bone marrow progenitor cells differentiate into CD49a+ NK cells. IL-15 was identified as being the key cytokine in this system that supported the development and maintenance of CD49a+ NK cells. The CD49a+ NK cells generated were Eomes−CD49b− and shared the same phenotype as hepatic trNK cells. IL-4 induced the expression of Eomes in generated NK cells and converted them into CD49a+Eomes+ cells, which were phenotypically and functionally similar to uterine trNK cells. Moreover, the IL-4/STAT6 axis was identified as being important in the generation of CD49a+Eomes+ induced NK cells. Collectively, these studies describe an approach to generate CD49a+Eomes−/+ subsets of NK cells and demonstrate important roles for IL-15 and IL-4 in the differentiation of these cells. These findings have potential for developmental research underlying the generation of different subsets of NK cells and the application of adoptive NK cell transfer therapies

Roles of the Siglec family in bone and bone homeostasis

Tremendous progress has been seen in the study of the role of sialic acid binding im-munoglobulin type lectins (Siglecs) in osteoimmunology in the past two decades. Interest in Siglecs as immune checkpoints has grown from the recognition that Siglecs have relevance to human disease. Siglecs play important roles in inflammation and cancer, and play key roles in immune cell signaling. By recognizing common sialic acid containing glycans on glycoproteins and glycolipids as regulatory receptors for immune cell signals, Siglecs are expressed on most immune cells and play important roles in normal homeostasis and self-tolerance. In this review, we describe the role that the siglec family plays in bone and bone homeostasis, including the regulation of osteoclast differentiation as well as recent advances in inflammation, cancer and osteoporosis. Particular emphasis is placed on the relevant functions of Siglecs in self-tolerance and as pattern recognition receptors in immune responses, thereby potentially providing emerging strategies for the treatment of bone related diseases