Immunoregulatory roles of eosinophils: a new look at a familiar cell

Abstract

Eosinophils are usually considered as end-stage degranulating effector cells of innate immunity. However, accumulating evidence has revealed additional roles for eosinophils that are immunoregulatory in nature in both the adaptive and innate arms of immunity. Specifically, eosinophils have key immunoregulatory roles as professional antigen-presenting cells and as modulators of CD4(+) T cell, dendritic cell, B cell, mast cell, neutrophil, and basophil functions. This review addresses the emerging immunoregulatory roles of eosinophils with a focus on recent data that support this new paradigm. Recognizing both the effector and immunoregulatory functions of eosinophils will enable a fuller understanding of the roles of eosinophils in allergic airways inflammation and may be pertinent to therapies that target eosinophils both for their acute and ongoing immunomodulatory functions.

Fig. 1

Illustration of a Model of Eosinophils as Antigen Presenting Cells. Eosinophils can be stimulated to express MHC Class II and co-stimulatory molecules by granulocyte-macrophage colony stimulating factor (GM-CSF) under experimental conditions. Eosinophils achieve the same expression of antigen presentation machinery in vivo in various disease states including asthma, chronic eosinophilic pneumonia, and parasitic infection. They then traffick to regional lymph nodes where they encounter CD4⁺ T cells, promoting proliferation and cytokine production (IL-4, IL-5, IL-13) by T cells.

Fig. 2

Illustration of a Model of Eosinophil Immunoregulation on CD4⁺ T cells. Eosinophils are capable of producing IL-12 and IL-4, which polarize T cells to Th1 cells and Th2 cells, respectively. Eosinophils express both Th1- and Th2-associated cytokines and chemokines. IL-25 is secreted by eosinophils and promotes Th2 activity. IL-4 has an amplifying effect on the Th2 response and promotes further eosinophil recruitment. IL-5 is a potent autocrine and paracrine growth and survival cytokine for eosinophils.