The dangerous liaison between iNKT cells and dendritic cells: does it prevent or promote autoimmune diseases?

Invariant natural killer T (iNKT) cells represent an important regulatory T-cell subset that perceives signals of danger and/or cellular distress and modulate the adaptive immune response accordingly. In the presence of pathogens, iNKT cells acquire an adjuvant function that is fundamental to boost anti-microbial and anti-tumor immunity. At the same time, iNKT cells can play a negative regulatory function to maintain peripheral T-cell tolerance toward self-antigens and to prevent autoimmune disease. Both these effects of iNKT cells involve the modulation of the activity of dendritic cells (DCs) through cell-cell interaction. Indeed, iNKT cells can either boost Th1 immunity by enhancing maturation of pro-inflammatory DCs or promote immune tolerance through the maturation of tolerogenic DCs. This dual action of iNKT cells opens questions on the modalities by which a single-cell subset can exert opposite effects on DCs and may even put in question the overall immunosuppressive properties of iNKT cells. This review presents the large body of evidence that shows the ability of iNKT cells to negatively regulate autoimmunity and to prevent autoimmune diseases including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. In addition, an update is provided on the mechanisms of iNKT-DCs interactions and how this can result in inflammatory or tolerogenic responses.