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Peripheral natural killer cell maturation depends on the transcription factor Aiolos
Author(s) -
Holmes Melissa L,
Huntington Nicholas D,
Thong Rebecca PL,
Brady Jason,
Hayakawa Yoshihiro,
Andoniou Christopher E,
Fleming Peter,
Shi Wei,
Smyth Gordon K,
DegliEsposti Mariapia A,
Belz Gabrielle T,
Kallies Axel,
Carotta Sebastian,
Smyth Mark J,
Nutt Stephen L
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201487900
Subject(s) - biology , lymphokine activated killer cell , natural killer cell , microbiology and biotechnology , innate lymphoid cell , interleukin 21 , interleukin 12 , cellular differentiation , immunology , immune system , t cell , innate immune system , cytotoxic t cell , gene , genetics , in vitro
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 CD 11b high CD 27 − 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 CD 27 − 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.