Mucosal Immunol. 2026 Apr 9:S1933-0219(26)00040-1. doi: 10.1016/j.mucimm.2026.04.003. Online ahead of print.
ABSTRACT
Innate lymphoid cells (ILCs) are distinct lineages defined by lineage-specifying transcription factors that drive their differentiation and effector programs. Despite being stable lineages, ILC plasticity has been reported. Plasticity is characterized by downregulation of the transcription factor that specifies the current ILC lineage, followed by upregulation of the transcription factor and surface markers that determine the phenotype of the ILC lineage it is acquiring. Even though NK cells rely on the lineage-specifying transcription factor Eomes, an unusual phenotype characterized by ILC1 marker expression was reported in the salivary glands and during Toxoplasma gondii infection. However, it remains unclear whether this reflects true ILC plasticity or simply phenotypic changes. Using a dual-reporter system that allows simultaneous detection of live expression and fate-labeling of Eomes, we observed downregulation of this lineage-specifying transcription factor in NK cells (Eomeslo cells) and upregulation of ILC1 markers in the salivary gland and multiple organs during Toxoplasma gondii infection, including organs that otherwise promote NK cell fate. While Eomeslo cells adopted an ILC1-like phenotype, they differentiated in the absence of Hobit, a pivotal transcription factor of ILC1s, distinguishing them from the ILC1 lineage. Therefore, our data demonstrate that NK cells can adopt an Eomeslo ILC1-like fate, even in the blood and secondary lymphoid organs, complementing previous findings on ILC2 and ILC3 plasticity towards the ILC1 lineage.
PMID:41966330 | DOI:10.1016/j.mucimm.2026.04.003