Research ResourceImmunology

In silico modeling identifies CD45 as a regulator of IL-2 synergy in the NKG2D-mediated activation of immature human NK cells

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Sci. Signal.  27 Jun 2017:
Vol. 10, Issue 485, eaai9062
DOI: 10.1126/scisignal.aai9062

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Searching for synergy

Natural killer (NK) cells detect and kill virally infected and transformed cells. NK cell activation depends on the balance between signaling by inhibitory and activating receptors, and cytokine signaling can synergize with activating receptor signaling to induce NK cell activation. Mukherjee et al. performed mass cytometry analysis of the abundances of more than 30 proteins and computational analysis of the relationships between those changes in abundance. The authors delineated the mechanism underlying the synergy between signaling by the cytokine interleukin-2 (IL-2) and subsequent stimulation of the activating receptor NKG2D in immature and mature subsets of human NK cells. This analysis predicted and experiments verified that the IL-2–stimulated increase in the abundance of the phosphatase CD45 in immature NK cells was the major determinant of the enhanced responses of these cells to NKG2D stimulation. The application of this type of analysis to other immune cell types will help to discover other synergies underlying cellular activation and function.