Lineage specific effector signatures of iNKT cells are shared amongst γδ T, innate lymphoid, and T helper cells

Abstract

Invariant natural killer T cells (iNKT) cells differentiate into three predominant effector lineages in the steady state. To understand these lineages, we sorted undifferentiated iNKT progenitor cells and each effector population, and analyzed their transcriptional profiles by RNAseq. Bioinformatic comparisons were made to effector subsets amongst other lymphocytes, specifically Th cells, innate lymphoid cells (ILC) and γδ 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-γ producing lineages such as Th1, ILC1, and intraepithelial γδ T cells. NKT2 and NKT17 cells were similar to their analogous subsets of γδ 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 antigen receptor specificity, suggesting the use of conserved regulatory cores for effector function.