Retinoid-X-Receptors (α/β) in Melanocytes Modulate Innate Immune Responses and Differentially Regulate Cell Survival following UV Irradiation Public Deposited

http://ir.library.oregonstate.edu/concern/articles/h128ng487

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  • Understanding the molecular mechanisms of ultraviolet (UV) induced melanoma formation is becoming crucial with more reported cases each year. Expression of type II nuclear receptor Retinoid-X-Receptor α (RXRα) is lost during melanoma progression in humans. Here, we observed that in mice with melanocyte-specific ablation of RXRα and RXRβ, melanocytes attract fewer IFN-γ secreting immune cells than in wild-type mice following acute UVR exposure, via altered expression of several chemoattractive and chemorepulsive chemokines/cytokines. Reduced IFN-γ in the microenvironment alters UVR-induced apoptosis, and due to this, the survival of surrounding dermal fibroblasts is significantly decreased in mice lacking RXRα/β. Interestingly, post-UVR survival of the melanocytes themselves is enhanced in the absence of RXRα/β. Loss of RXRs α/β specifically in the melanocytes results in an endogenous shift in homeostasis of pro- and anti-apoptotic genes in these cells and enhances their survival compared to the wild type melanocytes. Therefore, RXRs modulate post-UVR survival of dermal fibroblasts in a ‘‘non-cell autonomous’’ manner, underscoring their role in immune surveillance, while independently mediating post-UVR melanocyte survival in a ‘‘cell autonomous’’ manner. Our results emphasize a novel immunomodulatory role of melanocytes in controlling survival of neighboring cell types besides controlling their own, and identifies RXRs as potential targets for therapy against UV induced melanoma.
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  • Coleman DJ, Garcia G, Hyter S, Jang HS, Chagani S, et al. (2014) Retinoid-X-Receptors (α/β) in Melanocytes Modulate Innate Immune Responses and Differentially Regulate Cell Survival following UV Irradiation. PLoS Genetics 10(5): e1004321. doi:10.1371/journal.pgen.1004321
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  • description.provenance : Submitted by Erin Clark (erin.clark@oregonstate.edu) on 2014-07-08T19:35:28Z No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors.pdf: 15563615 bytes, checksum: c26d989981093c5b67dfd4731505da84 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors_SupportingInformation.zip: 14204479 bytes, checksum: 2d885fda83344bbb2857beca2573cc76 (MD5)
  • description.provenance : Made available in DSpace on 2014-07-08T19:35:51Z (GMT). No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors.pdf: 15563615 bytes, checksum: c26d989981093c5b67dfd4731505da84 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors_SupportingInformation.zip: 14204479 bytes, checksum: 2d885fda83344bbb2857beca2573cc76 (MD5) Previous issue date: 2014-05-08
  • description.provenance : Approved for entry into archive by Erin Clark(erin.clark@oregonstate.edu) on 2014-07-08T19:35:50Z (GMT) No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors.pdf: 15563615 bytes, checksum: c26d989981093c5b67dfd4731505da84 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors_SupportingInformation.zip: 14204479 bytes, checksum: 2d885fda83344bbb2857beca2573cc76 (MD5)

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