Lineage-Specific Effector Signatures of Invariant NKT Cells Are Shared amongst γδ T, Innate Lymphoid, and Th Cells

Invariant NKT cells differentiate into three predominant effector lineages in the steady state. To understand these lineages, we sorted undifferentiated invariant NK T progenitor cells and each effector population and analyzed their transcriptional profiles by RNAseq. Bioinformatic comparisons were made to effector subsets among other lymphocytes, specifically Th cells, innate lymphoid cells ( ILC), and gamma delta T cells. Myc-associated signature genes were enriched in NKT progenitors, like in other hematopoietic progenitors. Only NKT1 cells, but not NKT2 and NKT17 cells, had transcriptome similarity to NK cells and were also similar to other IFN-gamma-producing lineages such as Th1, ILC1, and intraepithelial gamma delta T cells. NKT2 and NKT17 cells were similar to their analogous subsets of gamma delta T cells and ILCs, but surprisingly, not to Th2 and Th17 cells. We identified a set of genes common to each effector lineage regardless of Ag receptor specificity, suggesting the use of conserved regulatory cores for effector function.