Figure 3.

Th17 cells in GVHD. Th17 cells traffic to the lung and skin by CCR6, where they mediate tissue damage. In the lung, Th17 cells secrete IL-17A, IL-17F, and TNF, which induce secretion of proinflammatory cytokines and chemokines by epithelial cells. Th17-derived cytokines act directly on neutrophils (neut), resulting in production of matrix metalloproteinases (MMPs), reactive oxygen species (ROS), and TNF. In the skin, IL-17A and IL-17F produced by infiltrating Th17 cells cause the production of several proinflammatory cytokines and chemokines by keratinocytes, resulting in further leukocyte recruitment and local tissue damage. IL-22 is secreted byTh17 cells and possibly Th22 cells activated by Langerhan cells (LCs). IL-22 induces keratinocyte proliferation, resulting in acanthosis and cutaneous GVHD pathology.