Harnessing the Therapeutic Potential of Th17 Cells

Figure 2

The heterogeneity of Th17 cell phenotype and functions. (a) In immunity to pathogens, (b) in tumour pathology, and (c) in promotion of autoimmune diseases. (a) Dendritic cells (DCs) are stimulated by pathogens to present antigens to induce the differentiation of naïve T-cells to Th17 cells. DCs produce IL-23 and IL-1β that facilitate the differentiation to and expansion of activated Th17 cells. Pathogen-specific Th17 cells produce IL-17 and, in some cases, IFNγ. IL-17 production induces IL-8 production by endothelial cells leading to neutrophil recruitment and pathogen eradication. Th17 cells can also recruit effector T cells for pathogen eradication. (b) Tumour microenvironments influence the phenotype of Th17 cells. TGFβ induces Th17 cells to produce vascular endothelia growth factor (VEGF) that induces angiogenesis. However, whilst IL-17 can promote tumour development, IFNγ produced by Th17 cells suppresses tumour development through recruitment of other immune cells. (c) IL-17 can promote chronic inflammation and autoimmune diseases. For example, Th17 cells infiltrate the blood brain barrier in patients with MS. In addition, IL-17 induces inflammation in dermal cells in patients with psoriasis. Furthermore, IL-17 can induce angiogenesis and the production of other cytokines-, proteases-, and the receptor activator of nuclear factor kappa-B ligand (RANK-L) from synoviocytes (SC) and osteoblasts (OB) in the synovium of RA patients activating osteoclasts (OC).

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