Genetic basis of the effects of ultraviolet light B on cutaneous immunity. Evidence that polymorphism at the Tnfa and Lps loci governs susceptibility.
The ability of local ultraviolet B (UVB) irradiation to impair the induction of dinitrofluorobenzene (DNFB)-specific contact hypersensitivity (CH) in mice has been shown to be genetically determined. We have explored the possibility that the mouse Tnfa and Lps loci are involved. We demonstrate that C3H/HeN (Lpsn) strains are UVB-susceptible, whereas C3H/HeJ (Lpsd) strains are UVB-resistant. Our results indicate that local intradermal (ID) injection of mouse recombinant tumor necrosis factor-alpha (TNFa) into sites painted with DNFB impaired the induction of CH, and in a dose response experiment the effect was found to be more marked in C3H/HeN than in C3H/HeJ. Systemic administration of neutralizing TNFa-specific antibody reconstituted the UVB-induced defect in induction of CH in UVB-susceptible mice, confirming that TNFa is a major mediator of the deleterious effects of UVB on induction of cutaneous immunity. The UVB-susceptibility trait (revealed by effects on CH) correlates positively with a recently described restriction fragment length polymorphism (RFLP) at the Tnfa locus (allele b) and with the wild-type Lpsn allele. These results suggest that appropriate alleles at the Tnfa and Lps loci conspire to render mice susceptible to the impairment of CH induction by UVB. We propose that the mechanism may function through the capacity of UVB to elicit excessive local (cutaneous) production of TNFa, which mediates the immune defect.
Yoshikawa
T
T
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33136.
Streilein
J W
JW
D000818:Animals; D002874:Chromosome Mapping; D003877:Dermatitis, Contact / Q000235:genetics*; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011110:Polymorphism, Genetic; D012867:Skin / Q000276:immunology / Q000528:radiation effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D006183:H-2 Antigens; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha