IL-17 and mucosal host defense

IL-17, a cytokine initially cloned from memory CD+ T cells, is produced by Th17 cells, a new lineage of T cells that are controlled by the transcription factor RORgt, as well as γ8 T cells, NK and NKT cells. IL-17A and IL-17F use both IL- 17RA and IL-17RC for signaling. IL-17RA is widely expressed in myeloid cells, fibroblasts, and epithelium. IL-17RA signaling is critical for mucosal immunity in the lung against extracellular bacterial infection through the regulation of granulopoietic growth factors and CXC chemokines required for neutrophil recruitment, as well as antimicrobial protein expression in epithelium. Although IL-17RA has a limited role in controlling the primary response to intracellular pathogens such as Listeria monocytogenes or Mycobacterium tuberculosis, other intracellular bacteria such as Francisella tularensis require IL-17 to mediate Th1 immunity. Furthermore, in the setting of vaccine-induced immunity, IL-17 regulates the recruitment of Th1 cells and is required for optimal vaccine responses for both extracellular and intracellular pathogens.