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Cell Death Dis. 2018 Aug 6;9(8):835. doi: 10.1038/s41419-018-0858-5.

Cbl-b deficiency provides protection against UVB-induced skin damage by modulating inflammatory gene signature.

Author information

1
Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.
2
Center for Medical Research, Medical University of Graz, Graz, Austria.
3
Inflammation Biology Section, Laboratory of Molecular Immunology, NIAID, NIH, Building 10, Room 11N112, 10 Center Drive, Bethesda, MD, 20892, USA.
4
Institute of Molecular Biotechnology (IMBA), Vienna, Austria.
5
Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria. peter.wolf@medunigraz.at.

Abstract

Exposure of skin to ultraviolet (UV) radiation induces DNA damage, inflammation, and immune suppression that ultimately lead to skin cancer. However, some of the pathways that regulate these events are poorly understood. We exposed mice to UVB to study its early effects in the absence of Cbl-b, a known suppressor of antitumor immune response in the skin. Cbl-b-/- mice were protected from UV-induced cell damage as shown by the lower number of cyclobutane pyrimidine dimers and sunburn cells in exposed skin compared to wild-type mice. Microarray data revealed that deficiency of Cbl-b resulted in differential expression of genes involved in apoptosis evasion, tumor suppression and cell survival in UV-exposed skin. After UVB, Cbl-b-/- mice upregulated gene expression pattern associated with regulation of epidermal cell proliferation linked to Wnt signaling mediators and enzymes that relate to cell removal and tissue remodeling like MMP12. Additionally, the skin of Cbl-b-/- mice was protected from chronic inflammatory responses and epidermal hyperplasia in a 4-weeks UVB treatment protocol. Overall, our results suggest a novel role for Cbl-b in regulating inflammation and physiologic clearance of damaged cells in response to UVB by modulating inflammatory gene signature.

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