Role of Th17 Cells in the Pathogenesis of Human IBD
Figure 2
T-cell differentiation into Th17 cells. Naive T cells, upon contact with antigen-presenting cells (APCs), have the potential to differentiate into Th1, Th2, Th17, and induced regulatory T cells (iTreg), a process controlled by the effector cytokines produced by APCs. Th17 cells are originated from a small subset of naive T cells that express CD161 and cytokine receptors IL-6R, TGFβR, IL-23R, IL-21R, and IL-1R, being their polarization into Th17 cells promoted by the combined activity of these cytokines. These cytokines mediate their effects by promoting or repressing the expression of different transcription factors, in particular STAT3 and RORt, which are critical for Th17 differentiation and development. It is of great interest to discern the nature of the APCs capable of inducing Th17 responses and the corresponding stimuli involved in this. Monocytes and circulating conventional DCs (cDCs) that produce large amounts of IL-1 and IL-6 when activated by lipopolysaccharide (LPS) and peptidoglycan are known to be the most efficient APCs for Th17 differentiation, whereas monocyte-derived DCs that produce IL-12, but not IL-1, in response to LPS or peptidoglycan fail to promote the differentiation of Th17 cells.
