Transcriptional control of liver-resident invariant Natural Killer cell development

We identify the existence of a putative LiNKT precursor that gives rise to LiNKT1 cells in a T-BET-dependent manner, a LiNKT17 subset in a BCL-6 and MAF-dependent manner, and a LiNKT2 subset in a BLIMP-1-dependent manner. The LiNKT1 subset differentiates into three additional subsets (LiNKT1.1, LiNKT1.2 and LiNKT1.3) and two effector LiNKT1.1 subsets.

Upon repetitive ligation of its TCR, the LiNKT2 subset expands and then transdifferentiates into a regulatory TR1-like LiNKT subset that has powerful local anti-inflammatory properties. Thus, the LiNKT cell pool is heterogeneous, composed of various transcriptionally distinct LiNKT subsets, and plastic.