Therapeutic manipulation of iNKT cells in autoimmunity: modes of action and potential risks.

Invariant NKT (iNKT) cells are a unique T cell subset that upon activation promptly produce copious amounts of pro- and anti-inflammatory cytokines, thereby contributing to both innate and acquired immunity. Animal models of autoimmune diseases suggest that iNKT cells favor immune regulation because their absence enhances autoimmunity in some models, whereas their enrichment alleviates autoimmune manifestations. Moreover, convergent experiments indicate that therapeutic targeting of iNKT cells can potentiate their immunoregulatory properties. Therefore, iNKT cells are considered an attractive target for the treatment of human autoimmune disorders. However, in our opinion several concerns must be addressed before iNKT cell manipulation can be safely used for treating patients with autoimmune diseases. Here, we discuss the therapeutic potential of this approach, and its possible pitfalls.