The role of ID3 in iNKT cell development (115.12)

Abstract

Abstract Invariant NKT cells comprise an unconventional T cell population with innate characteristics. Like the conventional αβ T cell lineage, they develop in the thymus from DP precursors after receiving TCR-dependent positive selection signals, although utilizing different pathways. iNKT cells further mature through a series of differentiation stages and acquire their effector properties intrathymically. The ID3 protein is required to reduce E protein activity for proper selection of DP progenitors towards conventional thymocyte lineages. Here, we investigate the requirement for ID3 in the thymic development of iNKT lineage, in vivo. We show that the frequency of iNKT cells in the Id3-/- thymus is higher than in WT littermates, in a cell-intrinsic manner. Id3-deficient post-selected DP cells express higher levels of the canonical Vα14-Jα18 TCRα chain transcripts. Additionally, the transcription factor PLZF, a molecular determinant of the NKT lineage, is expressed in a subset of post-selected DP cells in the Id3-/- mice. However, further thymic iNKT differentiation is blocked at an immature stage. Taken together these results suggest that ID3 restricts the innate T cell potential of DP precursors thus contributing to the lineage fate decisions at the DP stage. However, ID3 is necessary for the completion of the innate T cell program during iNKT differentiation. Ongoing gene expression analysis will identify potent E protein target genes essential for NKT development