Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor GATA3, which is further elevated specifically in ILC2s and T helper 2 cells to drive type-2 immunity during tissue repair, allergic disorders, and anti-helminth immunity. The control of this crucial up-regulation is poorly understood. Using CRISPR screens in ILCs we identified previously unappreciated myocyte-specific enhancer factor 2d (Mef2d)-mediated regulation of GATA3-dependent type-2 lymphocyte differentiation. Mef2d-deletion from ILC2s and/or T cells specifically protected against an allergen lung challenge. Mef2d repressed Regnase-1 endonuclease expression to enhance IL-33 receptor production and IL-33 signaling and acted downstream of calcium-mediated signaling to translocate NFAT1 to the nucleus to promote type-2 cytokine-mediated immunity.

中文翻译：

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Mef2d 增强 2 型免疫反应和过敏性肺部炎症


先天性淋巴细胞 (ILC) 和适应性 T 淋巴细胞可促进组织稳态和保护性免疫反应。它们的产生依赖于转录因子 GATA3，该因子在 ILC2 和 T 辅助 2 细胞中进一步升高，以在组织修复、过敏性疾病和抗蠕虫免疫过程中驱动 2 型免疫。人们对这种关键上调的控制知之甚少。在 ILC 中使用 CRISPR 筛选，我们发现了以前未被重视的肌细胞特异性增强因子 2d (Mef2d) 介导的 GATA3 依赖性 2 型淋巴细胞分化调节。 ILC2 和/或 T 细胞中的 Mef2d 缺失可专门防止过敏原肺部攻击。 Mef2d 抑制 Regnase-1 核酸内切酶的表达，以增强 IL-33 受体的产生和 IL-33 信号传导，并在钙介导的信号传导下游发挥作用，将 NFAT1 易位到细胞核，以促进 2 型细胞因子介导的免疫。