A Monoclonal Antibody to cis-Urocanic Acid Prevents the Ultraviolet-Induced Changes in Langerhans Cells and Delayed Hypersensitivity Responses in Mice, Although Not Preventing Dendritic Cell Accumulation in Lymph Nodes Draining the Site of Irradiation and Contact Hypersensitivity Responses

Abstract

Ultraviolet B (UVB) irradiation of C3H mice causes suppression of delayed hypersensitivity and contact hypersensitivity (CH) to antigens encountered following exposure, and is accompanied by a reduction in Langerhans cell (LC) numbers in the epidermis, loss of epidermal antigen-presenting cell function, and accumulation of dendritic cells in lymph nodes draining the site of irradiation. Various photoreceptors and mediators of these changes have been proposed, one of which is cis-urocanic acid (cis-UCA) formed from the naturally occurring trans-UCA in the epidermis on UV irradiation. A monoclonal antibody that reacts with cis-UCA has become available recently and has been used in this study to clarify the role of UCA. Pretreatment of C3H mice with the monoclonal antibody abrogated the UVB-induced and cis-UCA-induced reduction in epidermal LC numbers. It also prevented the UV-induced suppression of epidermal antigen-presenting cell ability as measured by the mixed skin lymphocyte response. However, it had no effect on the accumulation of dendritic cells in lymph nodes draining the site of UV exposure. With regard to hypersensitivity responses, it did not prevent UV-induced suppression of CH to oxazolone at a range of concentrations but it restored to normal the UV-suppressed delayed hypersensitivity to herpes simplex virus, if administered before exposure. Thus cis-UCA is involved in some UV-induced changes in murine skin but not in others, where alternative mediators, such as tumor necrosis factor-alpha, may be more important.

IL-12 Prevents the Inhibitory Effects of cis-Urocanic Acid on Tumor Antigen Presentation by Langerhans Cells: Implications for Photocarcinogenesis

“…A mAb with specificity cis-UCA was generated in BALB/c mice, as described by Norval and colleagues (24,25), and used as previously optimized. Mice were injected i.p.…”

Chromophore for UV‐lnduced Immunosuppression: Urocanic Acid

“…It has been shown recently that the reduction in the number after topical cis-UCA or UV irradiation could be abrogated by pretreatment of the mice with a monoclonal antibody specific for cis-UCA (12). In addition this effect could be blocked by pretreating the mice with neutralizing antibodies to tumor necrosis factor-a (TNF-a), leading to the hypothesis that cis-UCA formation following UV exposure could induce TNF-a expression by keratinocytes or by Langerhans cells, which would then mediate the reduction in the numbers of Langerhans cells (13).…”

“…Antigen-specific T cells were generated in the spleens of these animals, which were capable of transferring the suppression of DH to animals already infected with HSV (17). Pretreatment of the mice with an antibody to TNF-a did not abrogate the suppression (18), while pretreatment with the cis-UCA antibody led to the complete restoration of the DH response (12).…”

<i>cis</i>-Urocanic Acid Induces Mast Cell Degranulation and Release of Preformed TNF--α: A Possible Mechanism Linking UVB and <i>cis</i>-Urocanic Acid to Immunosuppression of Contact Hypersensitivity

“…Recently, it has been reported that C-UA has differential effects on the immunosuppression of delayed-type hypersensitivity versus CHR [19]. Antibodies to C-UA relieve UVB-induced suppression of delayed-type hypersensitivity [17] and reverse UV-induced changes in Langerhans cells but fail tu prevent CHR or accumulation of dendritic cells in the local draining lymph nodes [20]. In the experiments presented here, we sought to investigate the linkage between C-UA immunosuppression and mast cell degranulation [21].…”