Human basophils interact with memory T cells to augment Th17 responses

AbstractBasophils are a rare population of granulocytes that have long been associated with IgE-mediated and Th2-associated allergic diseases. However, the role of basophils in Th17 and/or Th1 diseases has not been reported. In the present study, we report that basophils can be detected in the mucosa of Th17-associated lung and inflammatory bowel disease and accumulate in inflamed colons containing large quantities of IL-33. We also demonstrate that circulating basophils increased memory Th17 responses. Accordingly, IL-3– or IL-33–activated basophils amplified IL-17 release in effector memory T cells (TEM), central memory T cells (TCM), and CCR6+ CD4 T cells. More specifically, basophils promoted the emergence of IL-17+IFN-γ− and IL-17+IFN-γ+, but not IL-17−IFN-γ+ CD4 T cells in TEM and TCM. Mechanistic analysis revealed that the enhancing effect of IL-17 production by basophils in TEM involved the ERK1/2 signaling pathway, occurred in a contact-independent manner, and was partially mediated by histamine via H2 and H4 histamine receptors. The results of the present study reveal a previously unknown function for basophils in augmenting Th17 and Th17/Th1 cytokine expression in memory CD4 T cells. Because basophils accumulated in inflamed inflammatory bowel disease tissues, we propose that these cells are key players in chronic inflammatory disorders beyond Th2.