Group-2 innate lymphoid cells (ILC2s), which are involved in type 2 inflammatory diseases such as allergy, can exhibit immunological memory, but the basis of this ILC2 "trained immunity" has remained unclear. Here, we found that stimulation with IL-33/IL-25 or exposure to the allergen papain induces the expression of the transcription factor c-Maf in mouse ILC2s. Chronic papain exposure results in high production of IL-5 and IL-13 cytokines and lung eosinophil recruitment, effects that are blocked by c-Maf deletion in ILCs. Transcriptomic analysis revealed that knockdown of c-Maf in ILC2s suppresses expression of type 2 cytokine genes, as well as of genes linked to a memory-like phenotype. Consistently, c-Maf was found highly expressed in human adult ILC2s but absent in cord blood and required for cytokine production in isolated human ILC2s. Furthermore, c-Maf-deficient mouse or human ILC2s failed to exhibit strengthened (“trained”) responses upon repeated challenge. Thus, the expression of c-Maf is indispensable for optimal type 2 cytokine production and proper memory-like responses in group-2 innate lymphoid cells.

中文翻译：

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c-Maf 促进细胞因子的产生并促进小鼠和人类 2 型先天性淋巴细胞中的记忆样反应

与过敏等 2 型炎症性疾病有关的第 2 组先天性淋巴细胞 (ILC2) 可以表现出免疫记忆，但这种 ILC2“经过训练的免疫”的基础仍不清楚。在这里，我们发现用 IL-33/IL-25 刺激或暴露于过敏原木瓜蛋白酶会诱导小鼠 ILC2 中转录因子 c-Maf 的表达。慢性木瓜蛋白酶暴露导致 IL-5 和 IL-13 细胞因子的大量产生和肺嗜酸性粒细胞募集，这些效应被 ILC 中的 c-Maf 缺失所阻断。转录组学分析显示，ILC2s 中 c-Maf 的敲低抑制了 2 型细胞因子基因的表达，以及与记忆样表型相关的基因的表达。始终如一，发现 c-Maf 在人类成人 ILC2 中高表达，但在脐带血中不存在，并且是分离的人类 ILC2 中细胞因子产生所必需的。此外，c-Maf 缺陷小鼠或人类 ILC2 在反复攻击后未能表现出增强（“训练”）的反应。因此，c-Maf 的表达对于第 2 组先天淋巴细胞中最佳 2 型细胞因子的产生和适当的记忆样反应是必不可少的。