title: An in vitro model of innate lymphoid cell function and differentiation.
abstract: Innate lymphoid cells (ILC) are RAG-independent lymphocytes with important roles in innate immunity, and include group-1 (natural killer (NK) cell, ILC1), group-2 (ILC2), and group-3 (lymphoid tissue inducer (LTi), NCR(+) ILC3) subsets. Group-3 ILC express Rorγt, produce interleukin (IL)-22, and are critically important in the normal function of mucosal tissues. Here, we describe a novel model cell line for the study of ILC function and differentiation. The parental MNK cell line, derived from NKR-P1B(+) fetal thymocytes, shows a capacity to differentiate in γc cytokines. One IL-7-responsive subline, designated MNK-3, expresses Rorγt and produces high levels of IL-22 in response to IL-23 and IL-1β stimulation. MNK-3 cells display surface markers and transcript expression characteristic of group-3 ILC, including IL-7Rα (CD127), c-kit (CD117), CCR6, Thy1 (CD90), RANK, RANKL, and lymphotoxin (LTα1β2). Using an in vitro assay of LTi cell activity, MNK-3 cells induce ICAM-1 and VCAM-1 expression on stromal cells in a manner dependent upon LTα1β2 expression. A second IL-2-responsive subline, MNK-1, expresses several NK cell receptors, perforin and granzymes, and shows some cytotoxic activity. Thus, MNK-1 cells serve as a model of ILC1/NK development and differentiation, whereas MNK-3 cells provide an attractive in vitro system to study the function of ILC3/LTi cells.
authors.affiliation: 1] Department of Immunology, University of Toronto, Toronto, Ontario, Canada [2] Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: D S J
authors.initials: DS
authors.lastname: Allan
authors.affiliation: 1] Department of Immunology, University of Toronto, Toronto, Ontario, Canada [2] Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Kirkham
authors.affiliation: 1] Department of Immunology, University of Toronto, Toronto, Ontario, Canada [2] Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: O A
authors.initials: OA
authors.lastname: Aguilar
authors.affiliation: 1] Department of Immunology, University of Toronto, Toronto, Ontario, Canada [2] Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: L C
authors.initials: LC
authors.lastname: Qu
authors.affiliation: 1] Department of Immunology, University of Toronto, Toronto, Ontario, Canada [2] Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.affiliation: 1] Department of Immunology, University of Toronto, Toronto, Ontario, Canada [2] Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: J H
authors.initials: JH
authors.lastname: Fine
authors.affiliation: 1] Department of Immunology, University of Toronto, Toronto, Ontario, Canada [2] Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Serra
authors.affiliation: 1] Department of Immunology, University of Toronto, Toronto, Ontario, Canada [2] Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Awong
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Gommerman
authors.affiliation: 1] Department of Immunology, University of Toronto, Toronto, Ontario, Canada [2] Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: J C
authors.initials: JC
authors.lastname: Zúñiga-Pflücker
authors.affiliation: 1] Department of Immunology, University of Toronto, Toronto, Ontario, Canada [2] Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: J R
authors.initials: JR
authors.lastname: Carlyle
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage; D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D016130:Immunophenotyping; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D055607:Receptors, Natural Killer Cell / Q000235:genetics / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D055607:Receptors, Natural Killer Cell