Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, Anhui, China.
Institue of Immunology, University of Science and Technology of China, Hefei, 230027, Anhui, China.
Nat Commun. 2018 Nov 19;9(1):4854. doi: 10.1038/s41467-018-07405-5.
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.
自然杀伤 (NK) 细胞被报道具有免疫记忆，CD49a 肝驻留 NK 细胞被证明能赋予半抗原特异性记忆反应，但这种记忆是如何诱导或维持的尚不清楚。在这里，我们表明表达 IL-7Rα 的记忆型 I 型固有淋巴细胞 (ILC1) 在淋巴结 (LN) 中产生，并需要 IL-7R 信号来维持其在肝脏中的寿命。半抗原敏化启动了 CXCR3 依赖性的 IL-7Rα ILC1 向皮肤引流 LNs 的募集，在那里它们被激活并获得半抗原特异性记忆潜能。然后，记忆 IL-7Rα ILC1 离开引流 LNs，并通过 CXCR6 优先招募到肝脏中驻留。此外，长期阻断 IL-7R 信号显著降低了 ILC1 介导的记忆反应。因此，我们的结果确定了记忆型 IL-7Rα ILC1 群体，并揭示了 LN-肝脏轴对于 ILC1 记忆产生和长期维持至关重要。
