IL-12 Prevents the Inhibitory Effects of cis -Urocanic Acid on Tumor Antigen Presentation by Langerhans Cells: Implications for Photocarcinogenesis
Open accessAbstract
UV radiation induces skin cancer primarily by its DNA-damaging properties, but also by its capacity to suppress the immune system. The photoisomer of urocanic acid (UCA), cis-UCA, is an important mediator of UV-induced immunosuppression and is involved in the inhibition of tumor immunity. The immunomodulatory cytokine IL-12 is known to counteract many of the immunosuppressive effects of UV radiation, including UV-induced immune tolerance. In this study, we addressed whether IL-12 also reverts the immunosuppressive activities of cis-UCA. Cis-UCA inhibits the ability of Langerhans cells to present tumor Ags for primary and secondary tumor immune responses. IL-12 treatment completely prevented the suppression by cis-UCA. IL-12 also protected mice from cis-UCA-induced suppression of contact hypersensitivity responses. To study the effects of cis-UCA on Ag-processing and Ag-presenting function in vitro, Langerhans cells were treated with UCA isomers and incubated with OVA or OVA peptide323–339 before exposure to OVA-specific transgenic T cells. Cis-, but not trans-UCA suppressed Ag presentation, which was completely reversed upon addition of IL-12. Since these findings suggest that cis-UCA may play an important role in photocarcinogenesis by inhibiting a tumor immune response, mice were chronically UVB irradiated to induce skin cancer. Whereas all mice in the control groups developed tumors, mice treated with a mAb with specificity for cis-UCA showed a significantly reduced tumor incidence. These data strongly indicate the importance of cis-UCA during photocarcinogenesis and support the concept of counteracting cis-UCA as an alternative strategy to prevent UV-induced skin cancer, possibly via the application of IL-12.
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UVR isomerizes trans-UCA to cis-UCA, which has potent immunosuppressive properties.
“UVR isomerizes trans-UCA to cis-UCA, which has potent immunosuppressive properties [58].”
From Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy (2013) · cites this paper as [58]
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“Improved memory function and motor learning by UV exposure was related to activation of the glutmate pathway in the brain, which was attributed to an increase in UCA [220].”
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“Infact pre-treatment with this cytokine completely reverted cis-uca immunosuppression in animal models and significantly reduced tumor development in chronic UV irradiation murine models [60].”
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“cis-urocanic acid has anti-cancer and promotes apoptosis (Beissert et al., 2001; Laihia et al., 2010).”
BackgroundLoss‐of‐function mutations in filaggrin gene and malignant melanoma: a case–control study
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- Authors
- Beissert, S., Rühlemann, D., Mohammad, T., Grabbe, S., El-Ghorr, A., Norval, M., Morrison, H., Granstein, R. D., & Schwarz, T.
- Affiliations
- University of Münster (DE)
- Department of Dermatology, University of Münster , Münster ,
- Purdue University West Lafayette (US)
- Department of Medical Microbiology, University of Edinburgh Medical School , Edinburgh ,
- University of Edinburgh (GB)
- Cornell University (US)
- Corresponding author
- Beissert, Stefan
- Grabbe, Stephan
- Schwarz, Thomas
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-12-01
- Volume
- 167
- Issue
- 11
- Pages
- 6232-6238
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1648039073
- Cited by
- 77
- References
- 48
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 1 · 2017: 4 · 2016: 2 · 2015: 3 · 2013: 6 · 2012: 2
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- cis-urocanic acid, IL-12, Langerhans cells, tumor antigen presentation, photocarcinogenesis, UV-induced immunosuppression, UVB-induced skin cancer, contact hypersensitivity, antitumor immunity, antigen processing
- MeSH terms
- Animals, Antigens, Neoplasm, Dermatitis, Contact, Female, Immune Sera, Immunization, Passive, Immunosuppressive Agents, Injections, Intraperitoneal, Langerhans Cells, Lymphocyte Activation, Mice, Inbred A, Mice, Inbred BALB C, Mice, Transgenic, Neoplasms, Radiation-Induced, Skin Neoplasms, T-Lymphocytes, Tumor Cells, Cultured, Ultraviolet Rays, Urocanic Acid, Antigen Presentation, Interleukin-12, Epitopes, T-Lymphocyte, Mice
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