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

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 naevus count in European-derived populations. We have characterized 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.

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

doi

10.1111/pcmr.12620

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

51-63

issue

1

eissn

1755-1471

issn

1755-148X

journal_volume

31

pub_type

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