Genetic variation in IRF4 expression modulates growth characteristics, tyrosinase expression and interferon-gamma response in melanocytic cells.

Genetic variation in IRF4 expression modulates growth characteristics, tyrosinase expression and interferon-gamma response in melanocytic cells.

Pigment Cell Melanoma Res. 2017 Jul 29;:

Authors: Chhabra Y, Yong HXL, Fane ME, Soogrim A, Lim W, Mahiuddin DN, Kim RSQ, Ashcroft M, Beatson SA, Ainger SA, Smit DJ, Jagirdar K, Walker GJ, Sturm RA, Smith AG

Abstract
A SNP within intron4 of the Interferon Regulatory Factor4 (IRF4) gene, rs12203592*C/T has been independently associated with pigmentation and age-specific effects on nevus count in European-derived populations. We have characterised the cis-regulatory activity of this intronic region and using human foreskin-derived melanoblast strains we have explored the correlation between IRF4 rs12203592 homozygous C/C and T/T genotypes with TYR enzyme activity, supporting its association with pigmentation traits. Further, higher IRF4 protein levels directed by the rs12203592*C allele were associated with increased basal proliferation but decreased cell viability following UVR, an etiological factor in melanoma development. Since UVR, and accompanying IFNγ-mediated inflammatory response is associated with melanomagenesis we evaluated its effects in the context of IRF4 status. Manipulation of IRF4 levels followed by IFNγ treatment revealed a subset of chemokines and immuno-evasive molecules that are sensitive to IRF4 expression level and genotype including CTLA4 and PD-L1. This article is protected by copyright. All rights reserved.

PMID: 28755520 [PubMed - as supplied by publisher]

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