In vivo availability of the cytokine IL-7 constrains the survival and homeostasis of peripheral iNKT cells.

Understanding the homeostatic mechanism of invariant natural killer T (iNKT) cells is a critical issue in iNKT cell biology. Because interleukin (IL)-15 is required for the thymic generation of iNKT cells, IL-15 has also been considered necessary for the homeostasis of peripheral iNKT cells. Here, we delineated the in vivo cytokine requirement for iNKT cells, and we came to the surprising conclusion that IL-7, not IL-15, is the homeostatic cytokine for iNKT cells.

Protein abundance of the cytokine receptor γc controls the thymic generation of innate-like T cells.

Innate-like T (iT) cells comprise a population of immunoregulatory T cells whose effector function is imposed during their development in the thymus to provide protective immunity prior to antigen encounter. The molecular mechanism that drives the generation of iT cells remains unclear. Here, we report that the cytokine receptor γc plays a previously unappreciated role for thymic iT cells by controlling their cellular abundance, lineage commitment, and subset differentiation.

Quantitative Difference in PLZF Protein Expression Determines iNKT Lineage Fate and Controls Innate CD8 T Cell Generation.

Zbtb16 encodes the zinc-finger protein PLZF, which is often used as a lineage marker for innate-like T cells and is specifically required for the generation of invariant natural killer T (iNKT) cells in the thymus. Here, we report that not only PLZF expression itself but also the relative abundance of PLZF proteins plays critical roles in iNKT cell development. Utilizing a Zbtb16 hypomorphic allele, PLZF, which produces PLZF proteins at only half of the level of the wild-type allele, we show that decreased PLZF expression results in a significant decrease in iNKT cell numbers, which is further associated with profound alterations in iNKT lineage choices and subset composition.

Immune quiescence in the oral mucosa is maintained by a uniquely large population of highly activated Foxp3 regulatory T cells.

The oral mucosa is a critical barrier tissue that protects the oral cavity against invading pathogens and foreign antigens. Interestingly, inflammation in the oral cavity is rarely observed, indicating that overt immune activation in this site is actively suppressed. Whether Foxp3 Treg cells are involved in controlling immunity of the oral mucosa, however, is not fully understood.