Frey Halle C, Sun Xin, Oudeif Fatima, Corona Darleny L, He Zijun, Won Taejoon, Schultz Tracy L, Carruthers Vern B, Laouar Amale, Laouar Yasmina
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Graduate Program of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
iScience. 2025 Feb 17;28(3):112043. doi: 10.1016/j.isci.2025.112043. eCollection 2025 Mar 21.
In an era where established lines between cell identities are blurred by intra-lineage plasticity, distinguishing stable from transitional states is critical, especially within Group 1 ILCs, where similarity and plasticity between NK cells and ILC1s obscure their unique contributions to immunity. This study leverages AsGM1-a membrane lipid associated with cytotoxic attributes absent in ILC1s-as a definitive criterion to discriminate between these cell types. Employing this glycosphingolipid signature, we achieved precise delineation of Group 1 ILC diversity across tissues. This lipid signature captured the binary classification of NK and ILC1 during acute liver injury and remained stable when tested in established models of NK-to-ILC1 plasticity driven by TGFβ or Toxoplasma gondii. The detection of AsGM1 at the iNK stage, prior to Eomes expression, and its persistence in known transitional states, positions AsGM1 as a pivotal marker for tracing NK-to-ILC1 transitions, effectively transcending the ambiguity inherent to the NK-to-ILC1 continuum.
在一个细胞身份之间既定界限因谱系内可塑性而变得模糊的时代，区分稳定状态和过渡状态至关重要，尤其是在第1组固有淋巴细胞（ILC）中，自然杀伤（NK）细胞和ILC1细胞之间的相似性和可塑性掩盖了它们对免疫的独特贡献。本研究利用AsGM1（一种与ILC1中不存在的细胞毒性属性相关的膜脂）作为区分这些细胞类型的决定性标准。利用这种糖鞘脂特征，我们实现了对跨组织的第1组ILC多样性的精确描绘。这种脂质特征在急性肝损伤期间捕捉到了NK细胞和ILC1细胞的二元分类，并且在由转化生长因子β（TGFβ）或刚地弓形虫驱动的NK细胞向ILC1细胞可塑性的既定模型中进行测试时保持稳定。在Eomes表达之前的初始NK（iNK）阶段检测到AsGM1，并且它在已知的过渡状态中持续存在，这使得AsGM1成为追踪NK细胞向ILC1细胞转变的关键标志物，有效地超越了NK细胞向ILC1细胞连续体固有的模糊性。
