title: Lineage relationships of human interleukin-22-producing CD56+ RORγt+ innate lymphoid cells and conventional natural killer cells.
abstract: Human interleukin (IL)-22-producing RORγt(+) innate lymphoid cells (ILC22) and conventional natural killer (cNK) cells are present in secondary lymphoid tissues. Both have an immunophenotype corresponding to stage III NK progenitors (CD56(+/-)CD117(high)CD94(-)). Using an in vitro differentiation and primary human tissues, we investigated their developmental relationships. cNK cells showed a CD56(+)CD117(+)CD7(+/-)LFA-1(high) phenotype and expressed surface receptors, cytokines, and transcription factors found on mature cNK cells. In contrast, ILC22 cells were contained within the CD56(+)CD117(high)CD94(-)CD7(-)LFA-1(-) fraction and produced IL-22, IL-8, and granulocyte macrophage colony stimulating factor. Although ILC22 cells expressed NKp44 and CD161, they lacked most other NK receptors and NK-associated transcription factors (T-bet and Eomes) and were incapable of interferon-γ production or cytotoxic responses. Most purified CD56(+)CD117(+)CD7(+/-)LFA-1(-) remained as ILC22 cells and never became cNK cells. In the absence of IL-15, CD34(+) cells showed a complete block in cNK differentiation and instead gave rise to a CD56(+) population of ILC22 cells. Conversely, in the absence of IL-7 and stem cell factor, cNK cells were generated but ILC22 cells showed minimal differentiation. Although human ILC22 cells and cNK progenitors have a phenotype that overlaps with stage III NK progenitors, they have unique cytokine requirements and can be distinguished by LFA-1 expression.
authors: Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA.
authors: Yong-Oon
authors: YO
authors: Ahn
authors: Bruce R
authors: BR
authors: Blazar
authors: Jeffrey S
authors: JS
authors: Miller
authors: Michael R
authors: MR
authors: Verneris
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D019002:CD56 Antigen; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018121:Receptors, Cytokine; D000097043:Interleukin-22