TH17 cytokines in autoimmune neuro-inflammation

It has been firmly established that IL-23 polarized TH17 cells are potent effectors in the pathogenesis of experimental autoimmune encephalitomyelitis (EAE). However, the relative importance of these cells in comparison to other encephalitogenic TH subsets, and the mechanisms that they employ to effect inflammatory demyelination, are topics of continuing investigation. Interestingly, deletion of individual ‘TH17 cytokines’, such as IL-17A, IL-17F, IL-22 and IL-21, does not phenocopy the complete EAE-resistance of IL-23-deficient mice. The instability of TH17 cells in vivo introduces an additional layer of complexity to their role in the context of relapsing or chronic disease. Recent data indicate that IL-23 drives the production of myeloid activating factors, such as GM-CSF, by myelin-reactive T cells and facilitates their accumulation in the CNS. This review discusses the above issues in relation to the use of TH17 cells and related factors as potential therapeutic targets and biomarkers in CNS autoimmune diseases such as multiple sclerosis (MS).

► Interleukin-23 polarized Th17 cells mediate autoimmune demyelinating disease. ► Th17 cells accumulate in the blood and central nervous system of individuals with MS. ► Paradoxically, encephalitogenicity is independent of IL-17 production. ► We discuss the putative mechanism of action of encephalitogenic Th17 cells.