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The latitude-dependent autoimmune disease risk genes ZMIZ1 and IRF8 regulate mononuclear phagocytic cell differentiation in response to vitamin D
- Source :
- Human molecular genetics. 28(2)
- Publication Year :
- 2018
-
Abstract
- Epidemiological, molecular and genetic studies have indicated that high serum vitamin D levels are associated with lower risk of several autoimmune diseases. The vitamin D receptor (VDR) binding sites in monocytes and dendritic cells (DCs) are more common in risk genes for diseases with latitude dependence than in risk genes for other diseases. The transcription factor genes Zinc finger MIZ domain-containing protein 1 (ZMIZ1) and interferon regulatory factor 8 (IRF8)-risk genes for many of these diseases-have VDR binding peaks co-incident with the risk single nucleotide polymorphisms (SNPs). We show these genes are responsive to vitamin D: ZMIZ1 expression increased and IRF8 expression decreased, and this response was affected by genotype in different cell subsets. The IL10/IL12 ratio in tolerogenic DCs increased with vitamin D. These data indicate that vitamin D regulation of ZMIZ1 and IRF8 in DCs and monocytes contribute to latitude-dependent autoimmune disease risk.
- Subjects :
- 0301 basic medicine
Vitamin
Single-nucleotide polymorphism
Biology
Calcitriol receptor
Monocytes
Autoimmune Diseases
03 medical and health sciences
chemistry.chemical_compound
Genetics
Vitamin D and neurology
medicine
Humans
Geography, Medical
Vitamin D
Molecular Biology
Gene
Genetics (clinical)
Cells, Cultured
Autoimmune disease
Cell Differentiation
General Medicine
Dendritic Cells
Vitamins
medicine.disease
Interleukin 10
030104 developmental biology
chemistry
Immunology
Interferon Regulatory Factors
IRF8
Transcription Factors
Subjects
Details
- ISSN :
- 14602083
- Volume :
- 28
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Human molecular genetics
- Accession number :
- edsair.doi.dedup.....5aad61e7d2cad9d7f69ee5832f627a72