Memory formation and long-term maintenance of IL-7Rα⁺ ILC1s via a lymph node-liver axis.

Abstract

Natural killer (NK) cells are reported to have immunological memory, with CD49a⁺ liver-resident NK cells shown to confer hapten-specific memory responses, but how this memory is induced or maintained is unclear. Here we show that memory type I innate lymphoid cells (ILC1s), which express IL-7Rα, are generated in the lymph nodes (LNs) and require IL-7R signaling to maintain their longevity in the liver. Hapten sensitization initiates CXCR3-dependent recruitment of IL-7Rα⁺ ILC1s into skin-draining LNs, where they are primed and acquire hapten-specific memory potential. Memory IL-7Rα⁺ ILC1s then exit draining LNs and are preferentially recruited, via CXCR6, to reside in the liver. Moreover, long-term blockade of IL-7R signaling significantly reduces ILC1-mediated memory responses. Thus, our results identify a memory IL-7Rα⁺ ILC1 population and reveal a LN-liver axis that is essential for ILC1 memory generation and long-term maintenance.