Title |
Peripheral natural killer cell maturation depends on the transcription factor Aiolos
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Published in |
EMBO Journal, October 2014
|
DOI | 10.15252/embj.201487900 |
Pubmed ID | |
Authors |
Melissa L Holmes, Nicholas D Huntington, Rebecca P L Thong, Jason Brady, Yoshihiro Hayakawa, Christopher E Andoniou, Peter Fleming, Wei Shi, Gordon K Smyth, Mariapia A Degli-Esposti, Gabrielle T Belz, Axel Kallies, Sebastian Carotta, Mark J Smyth, Stephen L Nutt |
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 CD11b(high)CD27(-) 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 33% |
Unknown | 2 | 67% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 1% |
Greece | 1 | 1% |
Germany | 1 | 1% |
Austria | 1 | 1% |
Unknown | 70 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 15 | 20% |
Researcher | 14 | 19% |
Student > Master | 9 | 12% |
Student > Bachelor | 6 | 8% |
Student > Doctoral Student | 4 | 5% |
Other | 10 | 14% |
Unknown | 16 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 20 | 27% |
Immunology and Microbiology | 14 | 19% |
Biochemistry, Genetics and Molecular Biology | 10 | 14% |
Medicine and Dentistry | 7 | 9% |
Engineering | 2 | 3% |
Other | 2 | 3% |
Unknown | 19 | 26% |