Peripheral natural killer cell maturation depends on the transcription factor Aiolos

Holmes, Melissa L., Huntington, Nicholas D., Thong, Rebecca P. L., Brady, Jason, Hayakawa, Yoshihiro, Andoniou, Christopher E., Fleming, Peter, Shi, Wei, Smyth, Gordon K., Degli-Esposti, Mariapia A., Belz, Gabrielle T., Kallies, Axel, Carotta, Sebastian, Smyth, Mark J. and Nutt, Stephen L. (2014) Peripheral natural killer cell maturation depends on the transcription factor Aiolos. EMBO Journal, 33 22: 2721-2734. doi:10.15252/embj.201487900

Author Holmes, Melissa L.
Huntington, Nicholas D.
Thong, Rebecca P. L.
Brady, Jason
Hayakawa, Yoshihiro
Andoniou, Christopher E.
Fleming, Peter
Shi, Wei
Smyth, Gordon K.
Degli-Esposti, Mariapia A.
Belz, Gabrielle T.
Kallies, Axel
Carotta, Sebastian
Smyth, Mark J.
Nutt, Stephen L.
Title Peripheral natural killer cell maturation depends on the transcription factor Aiolos
Journal name EMBO Journal   Check publisher's open access policy
ISSN 1460-2075
Publication date 2014-11-18
Year available 2014
Sub-type Article (original research)
DOI 10.15252/embj.201487900
Open Access Status DOI
Volume 33
Issue 22
Start page 2721
End page 2734
Total pages 14
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Natural killer (NK) cells are an innate lymphoid cell lineage characterized by their capacity to provide rapid effector functions, including cytokine production and cytotoxicity. Here, we identify the Ikaros family member, Aiolos, as a regulator of NK‐cell maturation. Aiolos expression is initiated at the point of lineage commitment and maintained throughout NK‐cell ontogeny. Analysis of cell surface markers representative of distinct stages of peripheral NK‐cell maturation revealed that Aiolos was required for the maturation in the spleen of CD11bhighCD27 NK cells. The differentiation block was intrinsic to the NK‐cell lineage and resembled that found in mice lacking either T‐bet or Blimp1; however, genetic analysis revealed that Aiolos acted independently of all other known regulators of NK‐cell differentiation. NK cells lacking Aiolos were strongly hyper‐reactive to a variety of NK‐cell‐mediated tumor models, yet impaired in controlling viral infection, suggesting a regulatory function for CD27 NK cells in balancing these two arms of the immune response. These data place Aiolos in the emerging gene regulatory network controlling NK‐cell maturation and function.
Keyword Differentiation
NK cell
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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