Figure 1

The scheme illustrates some of the inflammatory and anti-inflammatory pathways activated by Th17 cytokines in the gut. Antigen presenting cells (APC), such as dendritic cells and macrophages, respond to luminal antigens by producing cytokines, which promote the differentiation of naïve T helper (Th) cells in Th1 or Th17 cells. Th17 cells are, however, not stable and can convert to Th1 cells if they are stimulated by macrophage-derived (MØ) IL-12 and IL-23. In the gut of IBD patients, activated Th17 cells produce IL-17 (both A and F), IL-22, IL-26 and to a lesser extent IL-21, which is in contrast made preferentially by Th1 cells. IL-17 and IL-21 can induce stromal cells to secrete extracellular matrix-degrading proteases, such as matrix metalloproteinases (MMPs). IL-17A and IL-22 can exert anti-inflammatory effects due to their ability to stimulate anti-microbial peptides (that is defensins) and mucus secretion by epithelial cells. IFN-γ, a cytokine made by Th1 cells, can act on MØ and stimulate the production of other inflammatory cytokines, such as IL-1β and TNFα, which cooperate with Th17-type cytokines in promoting MMPs production by stromal cells.