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Differential Suppression of the Human Mixed Epidermal Cell Lymphocyte Reaction (MECLR) and Mixed Lymphocyte Reaction (MLR) by Cis‐Urocanic Acid

Abstract— Cis‐urocanic acid (UCA), formed in the stratum corneum by UV irradiation of trans‐UCA has been proposed as a mediator of UV‐induced immunosuppression in the skin. In this study, we examined the in vitro effect of cis‐UCA (6‐100 μg/mL) on the human mixed lymphocyte reaction (MLR) and the mixed epidermal cell lymphocyte reaction (MECLR). Addition of cis‐UCA (purified or in a mixture with trans‐UCA) did not affect the MLR but was able to induce a 20% suppression of the MECLR responses. Because this effect of cis‐UCA on the MECLR was not as strong as could be expected from previous in vivo results, we designed a set of experiments in order to enhance the in vitro immunosuppressive capacity of cis‐UCA. Firstly, we preincubated epidermal cells with UCA (50 u.g/mL) for 3 or 6 days before culture in the MECLR because in vivo repeated UV exposure can lead to a photostationary state, where cis‐UCA may be present for several weeks. This pretreatment with cis‐UCA resulted in a maximal decrease of the MECLR responses of 27%, whereas trans‐UCA had no effect. Secondly, we investigated whether UVB irradiation of epidermal cells could make cells more sensitive to cis‐UCA. However, addition of trans‐ or cis‐UCA did not potentiate the reduced alloac‐tivating capacity of UVB‐irradiated cells. Finally, we examined the possibility of a synergistic effect of cis‐UCA with histamine. Addition of histamine suppressed the MLR and MECLR responses, but neither cis‐ nor trans‐UCA were able to modulate this decrease. We conclude that cis‐UCA can partly downregulate the human MECLR but not the MLR. The mechanism involved in this differential downregulation is not known. In this respect it is striking that cis‐UCA does not potentiate the UVB‐ or histamine‐induced suppression of the MECLR.