Human basophils as effectors and immunomodulators of allergic inflammation and innate immunity

Abstract

Basophils have often stood in the shadow of their tissue-fixed mast cell counterparts which share some, common features, such as high-affinity IgE receptor expression and the ability to release histamine. That rodent mast cells produce a variety of pro-allergic and inflammatory cytokines has further added to the deception that basophils only play a minor role in allergic inflammation. Surprisingly, in humans, basophils, but not mast cells, appear to be the prime early producers of the Th2-type cytokines IL-4 and IL-13, which perform several crucial functions in initiating and maintaining allergic responses. This putative immunomodulatory role of basophils is supported further by their ability to express CD40 ligand, which, together with IL-4 and IL-13, serve as inductors of B-cell proliferation and class switching to IgE and IgG4. Moreover, human basophils are the main cellular source for rapid IL-4 generation, a mandatory requirement for the development of Th2 responses. Recent specific staining techniques have localised basophils in various tissues affected by allergic diseases and it appears likely, but remains to be proven, that the interaction of basophils, T cells and B cells at these sites propagate pro-allergic immune responses. Additionally, basophil activation is not restricted to antigen-specific IgE crosslinking but can be caused in non-sensitised individuals by parasitic antigens, plant lectins and viral superantigens binding to non-specific IgEs. Finally, the presence of novel IgE-independent receptor targets that cause trafficking and Th2 cytokine release from basophils further underlines their potential role in innate as well as adaptive immunity.

STAT5 in human basophils: IL‐3 is required for its FcεRI‐mediated phosphorylation

“…Basophils respond to various IgE-dependent and -independent stimuli and exert more than a simple bystander role in initiating and maintaining allergic reactions (1). Basophils are involved in the communication between immunocompetent cells such as macrophages, dendritic cells, T or B lymphocytes and exert major immunoregulatory functions, both in innate and adaptive immunity.…”

“…Basophils are involved in the communication between immunocompetent cells such as macrophages, dendritic cells, T or B lymphocytes and exert major immunoregulatory functions, both in innate and adaptive immunity. First, basophils are critical orchestrators of the Th2-type immune responses due to their capacity to generate Th2 polarizing cytokines (1)(2)(3). Second, they contribute to immunoglobulin synthesis and class switching, angiogenesis, autoimmunity, tumor immunity, and hematopoiesis (4,5).…”

Monocyte Cell Surface Glycosaminoglycans Positively Modulate IL-4-Induced Differentiation toward Dendritic Cells

“…It is produced by Th-type 2 cells in response to Ag receptor engagement and by basophils and mast cells upon cross-linking of the high-affinity receptor for IgE (1)(2)(3). IL-4 exerts its effects via the IL-4R of which two types have been identified that are composed of an IL-4R␣ chain and either a common ␥-chain (␥ c ; type I IL-4R) or an IL-13R␣1 chain (type II IL-4R) (4,5).…”

“…IL-4 is involved in tissue adhesion and inflammation as IL-4 up-regulates the expression of VCAM-1 and Eselectin on vascular endothelial cells and increases the adhesion of inflammatory cells to vascular endothelial cells (12). IL-4 acts on monocytes to differentiate them toward dendritic cells (DCs), 3 and is used in combination with GM-CSF to generate monocyte-derived DCs in vitro (13,14).…”

Mast cell activation syndromes: definition and classification

“…In addition, activated mast cells release newly synthesized membrane-derived (lipid) mediators of allergic reactions into the extracellular space. Blood basophils also participate in allergic and other inflammatory reactions in the same way as mast cells (1,8,9). However, not all allergic reactions involve both cell types, even if the reaction is systemic.…”