Identification of liver-specific CD24⁺ invariant NK T cells with low granzyme B production and high proliferative capacity

Invariant NK T (iNKT) cells are innate-like lymphocytes that can recognize the lipid Ag presented by MHC I like molecule CD1d. Distinct tissue distribution of iNKT cells subsets implies a contribution of these subsets to their related tissue regional immunity. iNKT cells are enriched in liver, an organ with unique immunological properties. Whether liver-specific iNKT cells exist and dedicate to the liver immunity remains elusive. Here, a liver-specific CD24⁺ iNKT subset is shown. Hepatic CD24⁺ iNKT cells show higher levels of proliferation, glucose metabolism, and mTOR activity comparing to CD24^- iNKT cells. Although CD24⁺ iNKT cells and CD24^- iNKT cells in the liver produce similar amounts of cytokines, the hepatic CD24⁺ iNKT cells exhibit lower granzyme B production. These liver-specific CD24⁺ iNKT cells are derived from thymus and differentiate into CD24⁺ iNKT in the liver microenvironment. Moreover, liver microenvironment induces the formation of CD24⁺ conventional T cells as well, and these cells exhibit higher proliferation ability but lower granzyme B production in comparison with CD24^- T cells. The results propose that liver microenvironment might induce the generation of liver-specific iNKT subset that might play an important role in maintaining liver homeostasis.