Key molecules in the differentiation and commitment program of T helper 17 (Th17) cells up-to-date

The mechanisms underlying autoimmunity and cancer remain elusive. However, perpendicular evidence has been evolved in the past decade that T helper (Th)17 cells and their related molecules are implicated in initiation and induction of various disease settings including both diseases. Meanwhile, extensive research on Th17 cells elucidated various molecules including cytokines and transcription factors as well as signaling pathways involved in the differentiation, maturation, survival and ultimate commitment of Th17 cells. In the current review, we revise the mechanistic underpinnings delivered by recent research on these molecules in the Th17 differentiation/commitment concert. We emphasize on those molecules proposed as targets for attaining potential therapies of various autoimmune disorders and cancer, aiming both at dampening the dark-side of Th17 repertoire and simultaneously potentiating its benefits in the roster of the antimicrobial response.

► Positive and negative transcription factors/cytokines in the differentiation/commitment of Th17 cells are well anticipated.
► TGF-β is a key element that orchestrates differentiation/commitment of Th17-Treg cells in both mice and human.
► mTOR signaling drives Th17 cell differentiation by mediating HIFα induction of Il17 transcription.
► Th17 cells pathogenicity depends on IL-1R/IL-23 signaling or on contact with APC according to their stimulation status.
► Plasticity is likely a normal trait of Th17 cells rendering them able to exert pathogenic or beneficial effects.