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.
Highlights
Innate lymphoid cells (ILCs) are a heterogeneous family of innate immune cells that are important for host defense and homeostasis[1,2,3,4]
We found that the expression of IL-7Rα by liver IL-7Rα+ ILC1s was enhanced after hapten sensitization (Fig. 1a and Supplementary Fig. 1a)
Further analysis revealed that there was a slight increase in liver IL-7Rα+ ILC1 numbers 96 h after sensitization (Supplementary Fig. 1d) and that the increase could last for at least 4 months (Supplementary Fig. 1e); expression of the proliferation marker, Ki67, in liver IL-7Rα+ ILC1s did not change, suggesting that the increase may be a consequence of cell migration, rather than local proliferation (Supplementary Fig. 1f)
Summary
Innate lymphoid cells (ILCs) are a heterogeneous family of innate immune cells that are important for host defense and homeostasis[1,2,3,4]. The first evidence supporting antigen-specific ILC memory came from studies by von Andrian and colleagues They reported that bulk liver NK cells ( referred to as group 1 ILCs), but not splenic NK cells, could induce hapten-specific skin contact hypersensitivity (CHS) responses, independent of T and B cells; the concept of NK cell memory was proposed[7]. Memory group 1 ILCs have not been described in human allergic contact dermatitis (ACD), human CD3−CD56highCD16− NK cells accumulate in the skin of patients with ACD18, suggesting the importance of group 1 ILCs in human allergic skin inflammation Despite such progress, the mechanisms underlying the formation and longterm maintenance of liver memory group 1 ILCs remain largely unknown. Our study sheds new light on the generation of ILC memory
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