Abstract
Natural killer (NK) cells were originally described as cytolytic effector cells, but since then have been recognized to possess regulatory functions on immune responses. Chemokines locate NK cells throughout the body in homeostatic and pathological conditions. They may also directly stimulate immune cells. CCL18 is a constitutive and inducible chemokine involved in allergic diseases. The aim of this study was to evaluate CCL18’s effect on NK cells from allergic and nonallergic donors in terms of both chemotactic and immune effects. Results showed that CCL18 was able to induce migration of NK cells from nonallergic donors in a G-protein-dependent manner, suggesting the involvement of a classical chemokine receptor from the family of seven-transmembrane domain G-protein-coupled receptors. In contrast, NK cells from allergic patients were unresponsive. Similarly, CCL18 was able to induce NK cell cytotoxicity only in nonallergic subjects. Purified NK cells did not express CCR8, one of the receptors described to be involved in CCL18 functions. Finally, the defect in CCL18 response by NK cells from allergic patients was unrelated to a defect in CCL18 binding to NK cells. Overall, our results suggest that some NK cell functions may be defective in allergic diseases.
Highlights
Natural killer (NK) cells belong to the family of innate lymphoid cells and are endowed with natural cytotoxicity against infected and cancer cells, as well as immunoregulatory functions [1]
While NK cells from allergic and nonallergic donors migrated toward the positive control CXCL12, only NK cells from nonallergic donors significantly migrated dose-dependently towards CC chemokine ligand 18 (CCL18) (Figure 1a)
We showed that NK cells from allergic donors cultured in medium alone for 24 and 48 h did not migrate in response to CCL18
Summary
Natural killer (NK) cells belong to the family of innate lymphoid cells and are endowed with natural cytotoxicity against infected and cancer cells, as well as immunoregulatory functions [1]. The role of NK cells in allergic diseases, including atopic dermatitis, rhinitis and allergic asthma, is increasingly studied but is still insufficiently understood [6,7]. In allergic asthma, some modifications in the human NK cell phenotype and functions have been shown either in blood or in peripheral tissues [5,8,9,10,11,12]. Patients with allergic asthma exhibit increased frequencies of IL-4-producing NK cells and decreased frequencies of IFN-γ-producing NK cells in the blood [9]. NK cells were found either to be proinflammatory [13,14], to have no effect [16], or to promote resolution of allergic inflammation [15]
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