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The latitude-dependent autoimmune disease risk genes ZMIZ1 and IRF8 regulate mononuclear phagocytic cell differentiation in response to vitamin D.

Parnell, Grant P; Schibeci, Stephen D; Fewings, Nicole L; Afrasiabi, Ali; Law, Samantha Pei Ling; Samaranayake, Shanuka; Kh'ng, Jing Hui; Fong, Yee Hsu; Brown, David A; Liddle, Christopher; Stewart, Graeme J; Booth, David R.
Hum Mol Genet; 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30285234
Epidemiological, molecular and genetic studies have indicated 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 ZMIZ1 and IRF8 - risk genes for many of these diseases - have VDR binding peaks co-incident with the risk 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.
Selo DaSilva