Targeting type II NKT cells for a novel therapeutic in lupus

Innate-like natural killer T (NKT) cells that recognize lipid antigens presented by CD1d molecules can be categorized as type I and type II. Although role for type I NKT cells has been investigated, involvement of type II NKT cells in lupus is not known. The enrichment of a self-glycolipid sulfatide and sulfatide/CD1d-tetramer+ type II NKT cells in kidney as well as sulfatide-mediated protection from disease in (NZB X NZW)F1 (BWF1) mice, prompted us to examine a novel hypothesis that type II NKT cells are immunoregulatory in SLE. The frequency, activation, and cytokine secretion phenotype of sulfatide/CD1d-tetramer+ cells during disease will be determined. The adoptive transfer of sulfatide/CD1d-tetramer+ cells as well as depletion of type II NKT will be carried out to examine their influence on the development of SLE. Lipid ligands for type II NKT cells, including cis-tetracosenoyl sulfatide and Miltefosine, a structural analog of lysophosphatidylcholine, will be used to treat disease in BWF1 mice. These studies will be important in not only understanding a key role of type II NKT cells in SLE pathogenesis but will also take a crucial step towards clinical studies for repurposing a drug as a potential therapeutic in SLE.