Basophils in pruritic skin diseases

Abstract

Basophils are rare cells in the peripheral blood which have the capability to infiltrate into the skin. Invasion of basophils has been detected in pruritic skin diseases, including atopic dermatitis, bullous pemphigoid, chronic spontaneous urticaria and contact dermatitis. In the skin, basophils are important players of the inflammatory immune response, as they release Th2 cytokines, including interleukin (IL)-4 and IL-13, subsequently inducing the early activation of T-cells. Further, basophils release a multitude of mediators, such as histamine and IL-31, which both play an important role in the initiation of the pruritic response via activation of sensory nerves. Chronic pruritus significantly affects the quality of life and the working capability of patients, though its mechanisms are not fully elucidated yet. Since basophils and neurons share many receptors and channels, bidirectional interaction mechanisms, which drive the sensation of itch, are highlighted in this review.

Keywords: IL-31; atopic dermatitis; basophils; neuro-immune interaction; pruritus.

Figure 1

Expression of receptors and release of cytokines in human basophils. Basophils interact with other immune cells and neurons through inflammatory mediators and receptor expressions. Interleukin (IL)-31, as well as its receptor complex consisting of the IL-31 receptor A and the oncostatin M receptor β, are expressed by basophils and contribute to pruritus. Stimulation with IL-31 leads to the secretion of the pro-inflammatory cytokines IL-4 and IL-13. Their respective receptors are IL-4R and IL-13R. Basophils express the high-affinity receptor FcϵRI. Upon crosslinking of the receptor with IgE, histamine is released, mediating itch. The hormone receptors are present on the cell surface, with the histamine 4 receptor being the most highly expressed. Activation of the neurokinin 1 receptor through substance P (SP) also causes histamine release. Basophils can be primed by IL-5, IL-3 and granulocyte macrophage-colony stimulating factor (GM-CSF). The respective receptors are CD125 and CD131 for IL-5, CD123 and CD131 for IL-3 and the GM-CSF receptor consists of GM-CSFRα and GM-CSFRβ. Activation of these receptors leads to increased histamine release. Another priming factor is nerve-growth factor, which binds to the tyrosine kinase A receptor on the cell surface. Basophils express the Mas-related G protein-coupled receptor X2 (MRGPRX2), which is part of the signaling cascade in inflammation and serves as a receptor for SP. Another pruritogen is thymic stromal lymphopoietin (TSLP), which binds to the TSLP receptor complex consisting of TSLP receptor and IL-7 receptor α and is proposed to cause itch. Whether basophils respond to TSLP is controversial. The lipid mediator sphingosine-1-phosphate (S1P) is stored in granules and its receptor S1P receptor 1 is expressed on the cell surface. It is proposed to have an anti-inflammatory effect on basophils. The leukotriene C4 (LTC4) is released by basophils and its receptor cysteinyl leukotriene receptor (LTCR) is expressed by basophils. GM-CSF: granulocyte macrophage-colony stimulating factor; GM-CSFRα: GM-CSF receptor α; GM-CSFRβ: GM-CSF receptor β; H1/H4: histamine 1/4 receptor; IL: interleukin; IL-4R: IL-4 receptor; IL-5R: IL-5 receptor; IL-7RA: IL-7 receptor α; IL-13R: IL13 receptor; IL-31RA: IL-31 receptor A; LTC4: leukotriene C4; LTCR: cysteinyl leukotriene receptor; MRGPRX2: Mas-related G protein-coupled receptor X2; NK1R: neurokinin 1 receptor; OSMRβ: oncostatin M receptor β; trkA: tyrosine kinase receptor A; TSLP: thymic stromal lymphopoietin; TSLPR: TSLP receptor; SP: substance P; S1P: sphingosine-1-phosphate; S1PR1: S1P receptor 1.