Figure 2: iNKT cell-mediated responses in the immune system. Several different antigenic GLs: microbial GLs; danger ligands as from cellular oxidation; and self antigens (in MS case they are myelin GLs) compete for binding to iTCR. The iTCR is a PRR that are ’pattern recognition receptors’ of the innate immune system. This recognition allows immune responses to different lipids–e.g. GLs, PLs and these can allow immune responses to microbial GLs (usually with high affinity) to overlap with those to self Ags (weaker affinity as a rule). The iNKT is 1) primed by the GL/iTCR/Cd1d receptor-located interaction or interface, and then 2) respond in one of several ways according to the environment, mainly cytokines-dependent. This affects control of diverse outcomes: i) pro-inflammatory (Th-1 type responses), ii) regulatory (Th-2 type responses) or iii) anti-pathogen (Th-17 type responses). Initial and subsequent interaction with IL-12 leads to iNKT pro-inflammatory functions. IL-12-activated iNKT mediate adjuvant activity by their production of IFN-?, which in turn activates both innate and acquired immune systems. In contrast, interaction with an IL-10-driven response generates regulatory Tr1 Treg (e.g. CD4+CD25+Foxp3) that are charged with development and maintaining tolerance. In addition to their roles in autoimmunity and tolerance, iNKT cells have also anti-pathogen activity triggered by IL-17 and IL-23. Adapted and modified from Taniguchi et al. [46].