Journal article

Peripheral natural killer cell maturation depends on the transcription factor Aiolos

ML Holmes, ND Huntington, RPL Thong, J Brady, Y Hayakawa, CE Andoniou, P Fleming, W Shi, GK Smyth, MA Degli-Esposti, GT Belz, A Kallies, S Carotta, MJ Smyth, SL Nutt

EMBO Journal | Published : 2014

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..

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Grants

Awarded by Australian Research Council


Funding Acknowledgements

We wish to thank K. Georgopoulos for the Ikzf3-deficient mice and J. Leahy and K. Elder for technical assistance. This work was supported by program and project grants from the NHMRC (1049407 to NDH 1027472 to SC and GTB575500 and APP1054925 to SLN). AK, GTB and SLN were supported by Australian Research Council Future Fellowships, and NDH, GKS, SC and MJS by a NHMRC Fellowships. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIIS.