An in vitro model of innate lymphoid cell function and differentiation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-03

AUTHORS

D S J Allan, C L Kirkham, O A Aguilar, L C Qu, P Chen, J H Fine, P Serra, G Awong, J L Gommerman, J C Zúñiga-Pflücker, J R Carlyle

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. More... »

PAGES

340

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/mi.2014.71

    DOI

    http://dx.doi.org/10.1038/mi.2014.71

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1010220614

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25138665


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