Basophils as Key Regulators of Allergic Inflammation and Th2-type Immunity

Abstract

Basophils have long been suspected as playing more than a bystander role in initiating and maintaining allergic disorders, despite their relatively low numbers compared with other effector cells, such as mast cells and eosinophils. In vitro studies clearly demonstrated their propensity to generate proallergic cytokines, such as interleukin 4 and interleukin 13, as well as histamine and leukotrienes after simulation with allergens and innate IgE-dependent triggers. However, only very recently have mouse basophils been identified as key regulators of allergy in vivo, including orchestrating Th2 immunity to protease allergens in the induction phase. This review highlights these exciting advances that go far in unraveling our understanding of basophil function in the orchestration of allergic inflammation.

Figure 1

Summary of human mast cell and basophil heterogeneity to stimulation and mediator generation (for better clarity, this is not a comprehensive list). Although both cell types react to IgE-mediated triggers, ionophores, basophils are more reactive to fMLP and C3a than most human mast cell types. Conversely, connective tissue mast cells (MC_TC), but not mucosal mast cells (MC_T) or basophils, are stimulated by neuropeptides and polybasic amines. In terms of mediator secretion, both cells secrete histamine and LTC₄. Mast cells additionally release tryptase as well as, in the case of MCTC, chymase and PGs (primarily PGD₂). Human basophils and mast cells differ in terms of cytokine synthesis: basophils are more restricted to IL-4 and IL-13 generation, whereas isolated mast cells produce TNF-a and IL-8 in vitro, although this may not reflect in vivo settings. Basophils are also known to respond to a large number of growth factors and chemokines that dramatically enhance their ability to generate mediators after IgE-dependent triggering. Human mast cells, on the other hand, are generally only responsive to priming by stem cell factor (SCF) and, to some extent, by IL-4 and IL-6. GM-CSF indicates granulocyte macrophage colony-stimulating factor; RANTES, regulated on activation normally T-cell expressed and secreted.

Figure 2

Simplified overview of the immunomodulatory roles of basophils. APC indicates antigen-presenting cells.