Fatty molecules needed for immune cell selection

A class of fatty molecules that are necessary for developing a unique set of early responding immune cells is identified in a paper published in Nature Immunology this week. These cells, called invariant natural killer T (iNKT) cells are capable of secreting large amounts of cytokines and can influence the responses of other immune cells. Previous work had shown that iNKT cells recognize a variety of microbial fatty molecules; however, the nature of self-generated fatty molecules that can be recognized by developing iNKT cells in the thymus has proved more controversial. Gennaro De Libero and colleagues show ether-bonded fat molecules select thymic iNKT cells. The team found that synthetic ether-bonded fatty molecules potently activated mature iNKT cells and promoted thymic iNKT development. They also noted that mice that lack GNPAT - the enzyme that generates these ether-bonded fats - produce considerably fewer iNKT cells and fail to accumulate these cells in peripheral tissues. Identification of the self-ligands recognized by iNKT cells will lead future efforts to understand rules that govern their development and survival.