A membrane lipid signature unravels the dynamic landscape of group 1 innate lymphoid cells across the health-disease continuum.

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.