Record Details
Retinoid-X-Receptors (α/β) in Melanocytes Modulate Innate Immune Responses and Differentially Regulate Cell Survival following UV Irradiation
ScholarsArchive at Oregon State University
| Field | Value |
|---|---|
| Title | Retinoid-X-Receptors (α/β) in Melanocytes Modulate Innate Immune Responses and Differentially Regulate Cell Survival following UV Irradiation |
| Names |
Coleman, Daniel J.
(creator) Garcia, Gloria (creator) Hyter, Stephen (creator) Jang, Hyo Sang (creator) Chagani, Sharmeen (creator) Liang, Xiaobo (creator) Larue, Lionel (creator) Ganguli-Indra, Gitali (creator) Indra, Arup K. (creator) |
| Date Issued | 2014-05-08 (iso8601) |
| Note | This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Public Library of Science. The published article can be found at: http://www.plosgenetics.org/. |
| Abstract | 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. |
| Genre | Article |
| Access Condition | http://creativecommons.org/licenses/by/3.0/us/ |
| Identifier | 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 |
