Role of STAT3 and consequences of its dysfunction in the differentiation of Th17 cells and defence against infection. Secretion of IL-1 and IL-6 by dendritic cells (DCs) under appropriate conditions results in Th17 differentiation. IL-6 is a STAT3-dependent cytokine that activates the transcription factor retinoic acid-related RORγt. Th17 cells secrete IL-17A, IL17-F and IL-22. IL-17A and IL-17F stimulate epithelial cells to produce chemokines that recruit polymorphonuclear leukocytes (PMNs) for killing of pathogens by phagocytosis. IL-22 secretion triggers the production of defensins by epithelial cells for further defence against extracellular pathogens. Mutations in STAT3 result in failure of Th17 differentiation, which, in turn, leads to susceptibility to fungi and extracellular bacteria.