Interleukin-12 bypasses common gamma-chain signalling in emergency natural killer cell lymphopoiesis
Ohs I, van den Broek M, Nussbaum K, Münz C, Arnold SJ, Quezada SA, Tugues S, Becher B.
Differentiation and homeostasis of natural killer (NK) cells relies on common gamma-chain(gc)-dependent cytokines, in particular IL-15. Consequently, NK cells do not develop in mice with targeted gc deletion. Herein we identify an alternative pathway of NK-cell development driven by the proinflammatory cytokine IL-12, which can occur independently of gc-signalling. In response to viral infection or upon exogenous administration, IL-12 is sufficient to elicit the emergence of a population of CD122þCD49bþ cells by targeting NK-cell precursors (NKPs) in the bone marrow (BM). We confirm the NK-cell identity of these cells by transcriptomewide analyses and their ability to eliminate tumour cells. Rather than using the conventional pathway of NK-cell development, IL-12-driven CD122þCD49bþ cells remain confined to a NK1.1lowNKp46low stage, but differentiate into NK1.1þNKp46þ cells in the presence of gc-cytokines. Our data reveal an IL-12-driven hard-wired pathway of emergency NK-cell lymphopoiesis bypassing steady-state gc-signalling.
