1,25-Dihydroxyvitamin D3 upregulates functional C-x-C chemokine receptor type 4 expression in human eosinophils

Epidemiological studies suggest that vitamin D may be protective against the inception and exacerbation of allergic diseases. However, the direct effect of vitamin D on eosinophils, the major effector cells in allergic inflammation, is not known. It has been reported that C-X-C chemokine receptor type 4 (CXCR4) in eosinophils is induced in non-Th2 cytokine milieu or in response to glucocorticoids, recruiting the cell to noninflammatory sites.

To test whether 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3) or calcitriol], the active metabolite of vitamin D, acts directly on eosinophils to induce upregulation of CXCR4.

Peripheral blood eosinophils from normal volunteers were isolated by CD16 immunomagnetic beads. Vitamin D receptor (VDR) expression was detected by RT-PCR. Eosinophils were cultured with 1,25-(OH)(2)D(3) and the survival and expression of CXCR4 on eosinophils were measured by flowcytometry. Eosinophil migration by CXCL-12/SDF-1 in the presence of 1,25-(OH)(2)D(3) was also analyzed.

Eosinophils expressed VDR. 1,25-(OH)(2)D(3) prolonged eosinophil survival and upregulated eosinophil surface expression of CXCR4 in a concentration-dependent manner. Interleukin (IL)-5 significantly reduced CXCR4 expression and migration induced by the ligand CXCL-12/SDF-1. 1,25-(OH)(2)D(3) reversed the negative effects of IL-5 on the CXCR4-CXCL12 pathway.

1,25-(OH)(2)D(3) regulates CXCR4 expression in eosinophils. The mechanism may be involved in eosinophil recruitment to noninflammatory sites where the ligand of CXCR4 is constitutively expressed.