The regulatory role of the thymic microenvironment during trafficking and differentiation of the invariant NKT (iNKT) cell lineage remains poorly understood. In this study, we show that fractalkine receptor expression marks emigrating subpopulations of the NKT1, NKT2, and NKT17 sublineages in the thymus and peripheral organs of naive mice. Moreover, NKT1 sublineage cells can be subdivided into two subsets, namely NKT1a and NKT1b, which exhibit distinct developmental and tissue-specific distribution profiles. More specifically, development and trafficking of the NKT1a subset are selectively dependent upon lymphotoxin (LT)alpha1beta2-LTbeta receptor-dependent differentiation of thymic stroma, whereas the NKT1b, NKT2, and NKT17 sublineages are not. Furthermore, we identify a potential cellular source for LTalpha1beta2 during thymic organogenesis, marked by expression of IL-7Ralpha, which promotes differentiation of the NKT1a subset in a noncell-autonomous manner. Collectively, we propose a mechanism by which thymic differentiation and retention of the NKT1 sublineage are developmentally coupled to LTalpha1beta2-LTbeta receptor-dependent thymic organogenesis.
Type of Publication:
Journal article published