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. 1994 Mar;81(3):352–358.

Characterization of the immunogenetic basis of ultraviolet-B light effects on contact hypersensitivity induction.

I Kurimoto 1, J W Streilein 1
PMCID: PMC1422343  PMID: 8206509

Abstract

Ultraviolet-B (UVB) light has proven to be deleterious to the skin immune system in mice, and one major consequence is impairment of the induction of contact hypersensitivity (CH) to haptens applied to UVB-exposed skin. It has been shown recently that the damaging effects of UVB on CH are mediated primarily by tumour necrosis factor-alpha (TNF-alpha). Moreover, not all strains of mice are equally susceptible to the deleterious effects of UVB. Mice that develop CH when hapten is applied to UVB-exposed skin are termed UVB-resistant (UVB-R), whereas mice that fail to acquire CH under these circumstances are termed UVB-susceptible (UVB-S). In the present experiments, we have characterized the UVB-susceptibility of numerous, genetically disparate inbred strains of mice by applying dinitrofluorobenzene (DNFB) epicutaneously to normal and to UVB-exposed body wall skin. The results indicate that the intensities of CH responses of these different strains were distributed in a bimodal fashion, with means at 92% and 28.5% of positive control responses. Among the strains with CH values distributed around the higher mean (i.e. UVB-R mice), the intensity of CH responses after UVB irradiation was uniformly greater than 75% of the intensity found among their positive controls. By contrast, among the strains with CH values distributed around the lower mean (i.e. UVB-S mice), the intensity of CH responses after UVB exposure was uniformly less than 60% of the intensity displayed by their positive controls. The phenotypic traits of UVB-S and UVB-R appear, therefore, to be genetically determined. To that end, we provide in this report additional evidence that UVB-S is a polygenically determined trait that is dictated by polymorphisms at a locus within H-2, and at the Lps locus. Resistance to UVB radiation is a recessive trait, and requires homozygosity of resistance alleles at one or both of the two participating loci, whereas UVB-S acts as a dominant trait. Among H-2 congenic strains of mice that are lipopolysaccharide (LPS)-sensitive (Lpsn), UVB radiation impaired the induction of CH to DNFB in all mice except those of the H-2d and H-2a haplotypes. Thus, UVB-susceptibility is dictated by alleles at two, independent genetic loci that can influence transcriptional and translational activity of the Tnf-alpha gene. The potential biological and medical meaning of regulatory polymorphisms governing TNF-alpha production in the skin may be revealed by the recent demonstration that UVB-susceptibility and UVB-resistance are phenotypic traits in humans.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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