期刊
IMMUNOLOGY
卷 150, 期 1, 页码 55-63出版社
WILEY-BLACKWELL
DOI: 10.1111/imm.12669
关键词
dendritic cells; macrophages; mitogen-activated protein kinase; monocytes; nuclear factor-kappa B; vitamin D
类别
资金
- Rosetrees Trust
- UK NIHR Biomedical Research Centre
- UK Medical Research Council [MC_EX_G0800785]
- MRC
- British Heart Foundation
- MRC [MC_EX_G0800785] Funding Source: UKRI
- Medical Research Council [MC_EX_G0800785] Funding Source: researchfish
- Rosetrees Trust [M71-F1] Funding Source: researchfish
Vitamin D is widely reported to inhibit innate immune signalling and dendritic cell (DC) maturation as a potential immunoregulatory mechanism. It is not known whether vitamin D has global or gene-specific effects on transcriptional responses downstream of innate immune stimulation, or whether vitamin D inhibition of innate immune signalling is common to different cells. We confirmed vitamin D inhibition of nuclear factor-jB (NF-kappa B) and p38 mitogen-activated protein kinase (MAPK) signalling in monocyte-derived DC (MDDC) stimulated with lipopolysaccharide (LPS). This was associated with global but modest attenuation of LPS-induced transcriptional changes at genome-wide level. Surprisingly, vitamin D did not inhibit innate immune NF-kappa B activation in monocytederived macrophages. Consistent with our findings in MDDC, ex vivo vitamin D treatment of primary peripheral blood myeloid DC also led to significant inhibition of LPS-inducible NF-kappa B activation. Unexpectedly, in the same samples, vitamin D enhanced activation of both NF-kappa B and MAPK signalling in primary peripheral blood monocytes. In a cross-sectional clinical cohort, we found no relationship between peripheral blood vitamin D levels and LPS-inducible activation of NF-kappa B and MAPK pathways in monocytes of myeloid DC. Remarkably, however, in vivo supplementation of people with vitamin D deficiency in this clinical cohort also enhanced LPS-inducible MAPK signalling in peripheral blood monocytes. Therefore, we report that vitamin D differentially modulates the molecular response to innate immune stimulation in monocytes, macrophages and dendritic cells. These results are of importance in the design of studies on vitamin D supplementation in infectious and immunological diseases.
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