Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the Epidermis
An important hallmark of radiation dermatitis is the impairment of the mitotic ability of the stem/progenitor cells in the basal cell layers due to radiation-induced DNA damage, leading to suppressed cell renewal in the epidermis. However, this mechanism alone does not adequately explain the complex...
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/6/3320 |
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| author | Claudia E. Rübe Benjamin M. Freyter Gargi Tewary Klaus Roemer Markus Hecht Christian Rübe |
| author_facet | Claudia E. Rübe Benjamin M. Freyter Gargi Tewary Klaus Roemer Markus Hecht Christian Rübe |
| author_sort | Claudia E. Rübe |
| collection | DOAJ |
| description | An important hallmark of radiation dermatitis is the impairment of the mitotic ability of the stem/progenitor cells in the basal cell layers due to radiation-induced DNA damage, leading to suppressed cell renewal in the epidermis. However, this mechanism alone does not adequately explain the complex pathogenesis of radiation-induced skin injury. In this review, we summarize the latest findings on the complex pathogenesis of radiation dermatitis and correlate these with the clinical features of radiation-induced skin reactions. The current studies show that skin exposure to ionizing radiation induces cellular senescence in the epidermal keratinocytes. As part of their epithelial stress response, these senescent keratinocytes secrete pro-inflammatory mediators, thereby triggering skin inflammation. Keratinocyte-derived cytokines and chemokines modulate intercellular communication with the immune cells, activating skin-resident and recruiting skin-infiltrating immune cells within the epidermis and dermis, thereby orchestrating the inflammatory response to radiation-induced tissue damage. The increased expression of specific chemoattractant chemokines leads to increased recruitment of neutrophils into the irradiated skin, where they release cytotoxic granules that are responsible for the exacerbation of an inflammatory state. Moreover, the importance of IL-17-expressing γδ-T cells to the radiation-induced hyperproliferation of keratinocytes was demonstrated, leading to reactive hyperplasia of the epidermis. Radiation-induced, reactive hyperproliferation of the keratinocytes disturbs the fine-tuned keratinization and cornification processes, leading to structural dysfunction of the epidermal barrier. In summary, in response to ionizing radiation, epidermal keratinocytes have important structural and immunoregulatory barrier functions in the skin, coordinating interacting immune responses to eliminate radiation-induced damage and to initiate the healing process. |
| first_indexed | 2024-04-24T18:11:42Z |
| format | Article |
| id | doaj.art-ba6462b49a884ee28ed7b2f91e93ee37 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T18:11:42Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ba6462b49a884ee28ed7b2f91e93ee372024-03-27T13:45:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01256332010.3390/ijms25063320Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the EpidermisClaudia E. Rübe0Benjamin M. Freyter1Gargi Tewary2Klaus Roemer3Markus Hecht4Christian Rübe5Department of Radiation Oncology, Saarland University Medical Center, 66421 Homburg, Saar, GermanyDepartment of Radiation Oncology, Saarland University Medical Center, 66421 Homburg, Saar, GermanyDepartment of Radiation Oncology, Saarland University Medical Center, 66421 Homburg, Saar, GermanyJosé Carreras Center, Internal Medicine, Saarland University Medical Center, 66421 Homburg, Saar, GermanyDepartment of Radiation Oncology, Saarland University Medical Center, 66421 Homburg, Saar, GermanyDepartment of Radiation Oncology, Saarland University Medical Center, 66421 Homburg, Saar, GermanyAn important hallmark of radiation dermatitis is the impairment of the mitotic ability of the stem/progenitor cells in the basal cell layers due to radiation-induced DNA damage, leading to suppressed cell renewal in the epidermis. However, this mechanism alone does not adequately explain the complex pathogenesis of radiation-induced skin injury. In this review, we summarize the latest findings on the complex pathogenesis of radiation dermatitis and correlate these with the clinical features of radiation-induced skin reactions. The current studies show that skin exposure to ionizing radiation induces cellular senescence in the epidermal keratinocytes. As part of their epithelial stress response, these senescent keratinocytes secrete pro-inflammatory mediators, thereby triggering skin inflammation. Keratinocyte-derived cytokines and chemokines modulate intercellular communication with the immune cells, activating skin-resident and recruiting skin-infiltrating immune cells within the epidermis and dermis, thereby orchestrating the inflammatory response to radiation-induced tissue damage. The increased expression of specific chemoattractant chemokines leads to increased recruitment of neutrophils into the irradiated skin, where they release cytotoxic granules that are responsible for the exacerbation of an inflammatory state. Moreover, the importance of IL-17-expressing γδ-T cells to the radiation-induced hyperproliferation of keratinocytes was demonstrated, leading to reactive hyperplasia of the epidermis. Radiation-induced, reactive hyperproliferation of the keratinocytes disturbs the fine-tuned keratinization and cornification processes, leading to structural dysfunction of the epidermal barrier. In summary, in response to ionizing radiation, epidermal keratinocytes have important structural and immunoregulatory barrier functions in the skin, coordinating interacting immune responses to eliminate radiation-induced damage and to initiate the healing process.https://www.mdpi.com/1422-0067/25/6/3320radiation dermatitisionizing radiationskin inflammationepidermiscellular senescencesenescence-associated secretory phenotype (SASP) |
| spellingShingle | Claudia E. Rübe Benjamin M. Freyter Gargi Tewary Klaus Roemer Markus Hecht Christian Rübe Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the Epidermis International Journal of Molecular Sciences radiation dermatitis ionizing radiation skin inflammation epidermis cellular senescence senescence-associated secretory phenotype (SASP) |
| title | Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the Epidermis |
| title_full | Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the Epidermis |
| title_fullStr | Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the Epidermis |
| title_full_unstemmed | Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the Epidermis |
| title_short | Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the Epidermis |
| title_sort | radiation dermatitis radiation induced effects on the structural and immunological barrier function of the epidermis |
| topic | radiation dermatitis ionizing radiation skin inflammation epidermis cellular senescence senescence-associated secretory phenotype (SASP) |
| url | https://www.mdpi.com/1422-0067/25/6/3320 |
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