title: Development of IL-22-producing NK lineage cells from umbilical cord blood hematopoietic stem cells in the absence of secondary lymphoid tissue.
abstract: Human secondary lymphoid tissues (SLTs) contain interleukin-22 (IL-22)-producing cells with an immature NK phenotype. Given their location, these cells are difficult to study. We have generated large numbers of NK22 cells from hematopoietic stem cells. HSC-derived NK22 cells show a CD56(+)CD117(high)CD94(-) phenotype, consistent with stage III NK progenitors. Like freshly isolated SLT stage III cells, HSC-derived NK22 cells express NKp44, CD161, CCR6, IL1 receptor, AHR, and ROR-γτ. IL-1β and IL-23 stimulation results in significant IL-22 but not interferon-γ production. Supernatant from these cells increases CD54 expression on mesenchymal stem cells. Thus, IL-22-producing NK cells can be generated in the absence of SLT. HSC-derived NK22 cells will be valuable in understanding this rare NK subset and create the opportunity for human translational clinical trials.
authors.affiliation: Division of Hematology/Oncology and Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Tang
authors.forename: Yong-Oon
authors.initials: YO
authors.lastname: Ahn
authors.forename: Peter
authors.initials: P
authors.lastname: Southern
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Jeffery S
authors.initials: JS
authors.lastname: Miller
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D019070:Cell Lineage / Q000276:immunology; D018920:Coculture Techniques / Q000379:methods; D005312:Fetal Blood / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007378:Interleukins / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism; D008099:Liver / Q000166:cytology; D008221:Lymphoid Tissue; D051379:Mice; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D019002:CD56 Antigen; D007378:Interleukins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D019009:Proto-Oncogene Proteins c-kit; D000097043:Interleukin-22; C497869:KLRD1 protein, human