Cytokines and growth factors produced and released by human eosinophils: lessons from cocultures and omics studies.

Besides their largely specific and abundant toxic granule proteins, their Charcot-Leyden crystals, DNA traps, and the release of leukotrienes, human eosinophils are often seen as affecting the immune response and tissue remodeling due to the release of numerous types of cytokines and growth factors. However, the extent of release and the functionality of such mediators, particularly from human eosinophils, remains uncertain. We review the literature focused on cocultures of human eosinophils with other cell types to identify possible cytokines and growth factors secreted by eosinophils and their function(s) on epithelial cells, fibroblasts, lymphocytes, and endothelial cells. Models of coculture include direct cell-to-cell contact, separation with filters, and the use of eosinophil-conditioned media. These models identified cytokines and growth factors as potential eosinophilic factors affecting the behavior of other cell types. In multiple published transcriptome data sets, the expression of these factors in eosinophils was confirmed using human blood and tissue eosinophils, which also allowed us to identify additional potentially important eosinophilic products. The findings in this review support the idea that human eosinophils remain effector cells via their release of toxic proteins (ie EPX/eosinophil peroxidase, RNASE3/eosinophil cationic protein, PRG2/eosinophil major basic protein), Charcot-Leyden crystals of galectin-10, DNA, and leukotrienes, and they produce and release a set of cytokines and growth factors to affect their surroundings.