Modulation of NK Cell Autocrine-Induced Eosinophil Chemotaxis by Interleukin-15 and Vitamin D_3: A Possible NK-Eosinophil Crosstalk via IL-8 in the Pathophysiology of Allergic Rhinitis

摘要

Natural killer cells (NK) secrete eosinophilotactic cytokines, however, whether they contribute to eosinophil chemotaxis by secreting IL-8 is not known. We investigated the ability of CD56+CD3-ve (NK cells) to induce chemotaxis of peripheral blood eosinophils from allergic rhinitis (AR) patients, through IL-8 secretion, and the effects of IL-15, the NK cell proactivating cytokine, and calcitriol: la, 25-dihydroxy Vitamin D_3 (vitamin D_3), the immunomodulator agent, in this scenario. Herein, it is shown that supernatants from unstimulated NK cells exhibited chemotactic activity against eosinophil. This effect was significantly augmented by IL-15 (1 ng/mL) treatment, resulting in an increase in the chemotactic index of approximately 3 folds and was abrogated by neutralizing antibody (Ab) to IL-8 in a dose-dependent fashion. The amount of IL-8 secreted by NK cells was increased by IL-15 treatment from levels of 88.64 +- 21.5 to 178.9 +- 23.6 Pg/mL and was significantly reduced by 10~(-2) M vitamin D_3 to levels of 59.2 +- 16.3 Pg/mL. Our results indicate a novel inflammatory crosstalk between NK cells and eosinophils via IL-15/IL-8 axis that can be modulated by vitamin D_3.