牛津大学Claus Nerlov小组近日取得一项新成果。经过不懈努力，他们研究出启动紧急2型骨髓形成的机制。这一研究成果于2026年3月11日发表在国际顶尖学术期刊《自然》上。

本研究表明，感染多螺线虫（Heligmosomoides polygyrthem）增加了EMPP对髓系命运的承诺，而牺牲了红细胞生成。感染H. polygyrthem后，IL-33报警蛋白在骨髓中积累，引导EMPPs上调GATA辅助因子LMO4，并优先分化为髓细胞。LMO4通过与GATA2相互作用，取代FOG1辅因子，并将GATA结合从巨核细胞-红细胞特异性重新分配到嗜碱性细胞、嗜酸性细胞和肥大细胞（BEM）特异性染色质，从而足以指导EMPPs的髓系命运。因此，携带GATA2突变的小鼠选择性地损害LMO4-GATA2相互作用，在GATA因子分配到BEM染色质、髓系谱系承诺、嗜碱性粒细胞和嗜酸性粒细胞产生以及寄生虫控制方面存在缺陷。这表明LMO4是IL-33调控的2型骨髓形成的主要调节因子，转录因子再分配是谱系承诺的机制。

据介绍，对寄生虫感染的免疫反应包括嗜碱性粒细胞和嗜酸性粒细胞的增加。这两种骨髓细胞类型在2型抗寄生虫免疫中起关键作用，并依赖GATA家族转录因子进行规范。嗜碱性粒细胞和嗜酸性粒细胞产生的第一步是从寡能红细胞引物多能祖细胞（EMPPs）生成嗜碱性-嗜酸性肥大细胞祖细胞（BEMPs）。然而，尚不清楚免疫反应如何作用于祖细胞启动2型骨髓形成。

附：英文原文

Title: A mechanism to initiate emergency type 2 myelopoiesis

Author: Fagnan, Alexandre, Di Genua, Cristina, Meng, Yiran, Drissen, Roy, Zhang, Zishan, Zhang, Bowen, Fallon, Padraic G., Pachnis, Vassilis, Mancini, Erika J., Progatzky, Frnze, Nerlov, Claus

Issue&Volume: 2026-03-11

Abstract: Immune responses to parasite infection involve the increased production of basophils and eosinophils. These two myeloid cell types have key roles in type 2 anti-parasite immunity1 and rely on GATA family transcription factors for their specification2,3. The first committed step in basophil and eosinophil production is generation of basophil–eosinophil–mast cell progenitors (BEMPs) from oligopotent erythroid-primed multipotent progenitors (EMPPs). However, it is not well established how immune responses act on progenitors to initiate type 2 myelopoiesis. Here we show that infection with the helminth Heligmosomoides polygyrus increases EMPP commitment to myeloid fate at the expense of erythropoiesis. Upon infection with H. polygyrus, the IL-33 alarmin accumulated in the bone marrow, causing EMPPs to upregulate the GATA co-factor LMO4 and preferentially differentiate into myeloid cells. LMO4 was sufficient to instruct myeloid fate in EMPPs by interacting with GATA2, displacing the FOG1 co-factor and redistributing GATA binding from megakaryocyte–erythroid-specific to basophil, eosinophil and mast cell (BEM)-specific chromatin. Accordingly, mice carrying a GATA2 mutation that selectively impairs the LMO4–GATA2 interaction were deficient in GATA factor allocation to BEM chromatin, myeloid lineage commitment, basophil and eosinophil production, and parasite control. This identifies LMO4 as an IL-33-regulated master regulator of type 2 myelopoiesis, and transcription factor reallocation as a mechanism of lineage commitment.

DOI: 10.1038/s41586-026-10256-6

Source: https://www.nature.com/articles/s41586-026-10256-6