Deleterious effects of cis-urocanic acid and UVB radiation on Langerhans cells and on induction of contact hypersensitivity are mediated by tumor necrosis factor-alpha.
Ultraviolet B (UVB) light disrupts epidermal Langerhans cells (LC) universally and impairs the induction of contact hypersensitivity (CH) to epicutaneously applied haptens in certain strains of mice. Similar effects are observed when tumor necrosis factor-alpha (TNF alpha) is injected intradermally (ID) in mice. Trans-urocanic acid (UCA), a photoreceptor for UVB radiation, is known to be immunosuppressive. To determine whether cis-UCA is important in the process by which UVB and/or TNF alpha act in the skin, cis-UCA was injected ID into C57BL/6, C3H/HeN, BALB/c, and C3H/HeJ mice. Whole mounts of epidermis were removed 5 h later and stained immunochemically with anti-Ia antibodies. Microscopy revealed that Ia-bearing LC had lost their dendrites, had rounded up, and were reduced in number in all strains examined. Moreover, when dinitrofluorobenzene (DNFB) was applied epicutaneously to the injected site, induction of CH was grossly impaired. When neutralizing anti-TNF alpha antibodies were administered intraperitoneally 2 h prior to ID injection of cis-UCA, the deleterious effects on LC and CH induction were largely reversed. These results indicate that the actions of cis-UCA on LC and on CH induction are very similar to those achieved by ID injections of TNF alpha and by cutaneous exposure to low-dose UVB. Because the effects of UVB radiation and cis-UCA are reversed by anti-TNF alpha antibodies, we propose that UVB radiation impairs the induction of CH in mice by converting trans-UCA to cis-UCA within the epidermis; cis-UCA in turn causes the local release of TNF alpha, which thwarts sensitization by its ability to alter the functional program of epidermal Langerhans cells, thereby preventing the induction of CH.
Kurimoto
I
I
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101.
Streilein
J W
JW
D000287:Administration, Topical; D000818:Animals; D003877:Dermatitis, Contact / Q000209:etiology*; D004139:Dinitrofluorobenzene / Q000008:administration & dosage; D007271:Injections, Intradermal; D007801:Langerhans Cells / Q000187:drug effects* / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013237:Stereoisomerism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D004139:Dinitrofluorobenzene; D014560:Urocanic Acid