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J Exp Med. 2020 Apr 6;217(4). pii: e20190549. doi: 10.1084/jem.20190549.

Cell-intrinsic adrenergic signaling controls the adaptive NK cell response to viral infection.

Author information

Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY.
Division of Animal Physiology and Immunology, Technical University of Munich, Freising, Germany.
Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY.


Natural killer (NK) cells are innate lymphocytes that exhibit adaptive features, such as clonal expansion and memory, during viral infection. Although activating receptor engagement and proinflammatory cytokines are required to drive NK cell clonal expansion, additional stimulatory signals controlling their proliferation remain to be discovered. Here, we describe one such signal that is provided by the adrenergic nervous system, and demonstrate that cell-intrinsic adrenergic signaling is required for optimal adaptive NK cell responses. Early during mouse cytomegalovirus (MCMV) infection, NK cells up-regulated Adrb2 (which encodes the β2-adrenergic receptor), a process dependent on IL-12 and STAT4 signaling. NK cell-specific deletion of Adrb2 resulted in impaired NK cell expansion and memory during MCMV challenge, in part due to a diminished proliferative capacity. As a result, NK cell-intrinsic adrenergic signaling was required for protection against MCMV. Taken together, we propose a novel role for the adrenergic nervous system in regulating circulating lymphocyte responses to viral infection.


Conflict of interest statement

Disclosures: The authors declare no competing interests exist.

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