小柯机器人

英国MRC分子生物学实验室Andrew N. J. McKenzie研究小组发现，Mef2d能增强2型免疫反应和过敏性肺部炎症。2024年6月28日，国际知名学术期刊《科学》发表了这一成果。

通过在先天性淋巴细胞（ILC）中进行CRISPR筛选，研究人员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型淋巴细胞分化调控。从ILC2和/或T细胞中缺失Mef2d可特异性地抵御过敏原的肺部挑战。Mef2d抑制了Regnase-1内切酶的表达，从而增强了IL-33受体的产生和IL-33的信号传导，并在钙介导的信号传导下游发挥作用，将NFAT1转位到细胞核，以促进2型细胞因子介导的免疫。

据了解，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，在组织修复、过敏性疾病和抗蠕虫免疫过程中，GATA3在ILC2和T辅助2细胞中特异性地进一步升高，以驱动2型免疫。人们对这种关键性上调的控制还知之甚少。

附：英文原文

Title: Mef2d potentiates type-2 immune responses and allergic lung inflammation

Author: Aydan C. H. Szeto, Paula A. Clark, Ana C. F. Ferreira, Morgan Heycock, Emma L. Griffiths, Eric Jou, Jonathan Mannion, Shi-Lu Luan, Sophie Storrar, Martin D. Knolle, Patrycja Kozik, Helen E. Jolin, Padraic G. Fallon, Andrew N. J. McKenzie

Issue&Volume: 2024-06-28

Abstract: 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.

DOI: adl0370

Source: https://www.science.org/doi/10.1126/science.adl0370