Eosinophils Mediate Basophil-Dependent Allergic Skin Inflammation in Mice.

The mechanisms leading to allergic skin inflammation, such as atopic dermatitis or urticaria, are poorly defined. Here we used a mouse model for IgE-dependent chronic allergic inflammation to study the role of basophils and eosinophils for induction of pathology. FcεRI expression in basophils was required for the ear swelling response, and basophils promoted the expression of eosinophil-recruiting chemokines in the ear. The ear swelling response could be prevented by prior infection of mice with helminths in an IgE-dependent manner. Impaired skin eosinophilia and reduced ear swelling was further observed in IL-4/IL-13-deficient and STAT6-deficient mice. In addition, eosinophil-deficient ΔdblGATA mice showed only weak ear swelling response, which could be enhanced by eosinophil transfer. This suggests that IgE-activated basophils orchestrate the recruitment of eosinophils by secretion of IL-4/IL-13, which leads to STAT6-dependent expression of CCL24 from endothelial cells and extravasation of eosinophils into the ear pinna. Eosinophils are then the critical effector cells that cause pathology. Therefore, combined therapeutic approaches that block basophil activation and reduce eosinophil numbers could be efficient strategies to improve treatment of chronic allergic disorders of the skin.

Role of basophils in protective immunity to parasitic infections.

Basophils have been recognized as important players for protective immunity against a variety of different endo- and ectoparasites. Although basophils represent a relatively rare and short-lived cell type, they produce large quantities of effector molecules including histamine, cytokines, chemokines, and lipid mediators which promote type 2 immune responses. Basophils can be activated either directly by parasite-derived factors or indirectly by recognition of parasite-derived antigens via IgE bound to its high-affinity receptor FcεRI on the cell surface. Many parasitic infections cause expansion and tissue recruitment of basophils, but the role of basophils for protective immunity remains poorly understood. The development of basophil-deficient mouse models over the past few years makes it possible to study their contributions in various infections. We review here the current knowledge regarding the role of basophils for protective or immunomodulatory functions of basophils mainly during infections of mice with protozoan parasites, helminths, and ectoparasites.

Basophils in inflammation.

Basophils are functionally closely related to mast cells. Both cell types express the high-affinity IgE receptor (FcεRI) and rapidly release preformed mediator from intracellular stores upon IgE-mediated activation. However, in contrast to mast cells basophils finish their maturation in the bone marrow and have a lifespan of only 2-3 days. Basophil numbers increase in response to IL-3 or TSLP and migrate into tissues to promote type 2 immune responses. Here we review recent advances regarding the pro- and anti-inflammatory functions of basophils in murine models and human allergic inflammation of the skin, lung and intestine.