title: Different NK cell developmental events require different levels of IL-15 trans-presentation.
abstract: NK cell development requires IL-15, which is "trans-presented" to IL-15Rβγ on NK cells by IL-15Rα on other cells. In this study, we report that different levels of IL-15 trans-presentation are required for different NK cell developmental events to reach full maturation status. Because the IL-15Rα intracellular domain has the capacity to recruit signaling molecules, we generated knockin and transgenic (Tg) mice that lack the intracellular domain to assess the role of the IL-15 trans-presentation level independent of the function of this domain. The level of IL-15Rα on various cells of these mice follows the order WT > Tg6 > knockin > Tg1 ≥ knockout. Bone marrow (BM)-derived dendritic cells prepared from these mice induced Stat5 phosphorylation in NK cells. The level of phospho-Stat5 correlated with the level of IL-15Rα on BMDCs, thus offering the opportunity to study quantitative effects of IL-15 trans-presentation on NK cell development in vivo. We found that NK cell homeostasis, mature NK cell differentiation, and acquisition of Ly49 receptor and effector functions require different levels of IL-15 trans-presentation input to achieve full status. All NK cell developmental events examined were quantitatively regulated by the IL-15Rα level of BM-derived and radiation-resistant accessory cells, but not by IL-15Rα of NK cells. We also found that IL-15Rα of radiation-resistant cells was more potent than IL-15Rα of BM-derived accessory cells in support of stage 2 to stage 3 splenic mNK differentiation. In summary, each examined developmental event required a particular level of IL-15 trans-presentation by accessory cells.
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Gilbert Aaron
authors.initials: GA
authors.lastname: Lee
authors.forename: Yae-Huei
authors.initials: YH
authors.lastname: Liou
authors.forename: Szu-Wen
authors.initials: SW
authors.lastname: Wang
authors.forename: Kai-Liang
authors.initials: KL
authors.lastname: Ko
authors.forename: Si-Tse
authors.initials: ST
authors.lastname: Jiang
authors.forename: Nan-Shih
authors.initials: NS
authors.lastname: Liao
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D055879:Gene Knock-In Techniques; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D019409:Interleukin-15 / Q000378:metabolism* / Q000502:physiology; D053720:Interleukin-15 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000378:metabolism
chemical_list: D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D055650:NK Cell Lectin-Like Receptor Subfamily A