Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune Suppression
Type I interferons (IFNs) are important enhancers of immune responses which are downregulated in human cancers, including skin cancer. Solar ultraviolet (UV) B radiation is a proven environmental carcinogen, and its exposure contributes to the high prevalence of skin cancer. The carcinogenic effects...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1822 |
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| author | Mohammad Asif Sherwani Israr Ahmad Monica J. Lewis Ahmed Abdelgawad Harunur Rashid Kevin Yang Ching-Yi Chen Chander Raman Craig A. Elmets Nabiha Yusuf |
| author_facet | Mohammad Asif Sherwani Israr Ahmad Monica J. Lewis Ahmed Abdelgawad Harunur Rashid Kevin Yang Ching-Yi Chen Chander Raman Craig A. Elmets Nabiha Yusuf |
| author_sort | Mohammad Asif Sherwani |
| collection | DOAJ |
| description | Type I interferons (IFNs) are important enhancers of immune responses which are downregulated in human cancers, including skin cancer. Solar ultraviolet (UV) B radiation is a proven environmental carcinogen, and its exposure contributes to the high prevalence of skin cancer. The carcinogenic effects of UV light can be attributed to the formation of cyclobutane pyrimidine dimers (CPD) and errors in the repair and replication of DNA. Treatment with a single dose of UVB (100 mJ/cm<sup>2</sup>) upregulated IFNα and IFNβ in the skin of C57BL/6 mice. IFNα and IFNβ were predominantly produced by CD11b+ cells. In mice lacking the type I IFN receptor 1 (IFNAR1), the repair of CPD following cutaneous exposure to a single dose of UVB (100 mJ/cm<sup>2</sup>) was decreased. UVB induced the expression of the DNA repair gene xeroderma pigmentosum A (<i>XPA</i>) in wild-type (WT) mice. In contrast, such treatment in IFNAR1 (<i>IFNAR1-/-</i>) mice downregulated <i>XPA</i>. A local UVB regimen consisting of UVB radiation (150 mJ/cm<sup>2</sup>) for 4 days followed by sensitization with hapten 2,4, dinitrofluorobenzene (DNFB) resulted in significant suppression of immune responses in both WT and <i>IFNAR1-/-</i> mice. However, there were significantly higher CD4+CD25+Foxp3+ regulatory T-cells in the draining lymph nodes of <i>IFNAR1-/-</i> mice in comparison to WT mice. Overall, our studies reveal a previously unknown action of type I IFNs in the repair of photodamage and the prevention of UVB-induced immune suppression. |
| first_indexed | 2024-03-09T23:43:45Z |
| format | Article |
| id | doaj.art-5452502a469d4d0aabb4b9886db91396 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:43:45Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5452502a469d4d0aabb4b9886db913962023-11-23T16:47:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01233182210.3390/ijms23031822Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune SuppressionMohammad Asif Sherwani0Israr Ahmad1Monica J. Lewis2Ahmed Abdelgawad3Harunur Rashid4Kevin Yang5Ching-Yi Chen6Chander Raman7Craig A. Elmets8Nabiha Yusuf9Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USADivision of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USAType I interferons (IFNs) are important enhancers of immune responses which are downregulated in human cancers, including skin cancer. Solar ultraviolet (UV) B radiation is a proven environmental carcinogen, and its exposure contributes to the high prevalence of skin cancer. The carcinogenic effects of UV light can be attributed to the formation of cyclobutane pyrimidine dimers (CPD) and errors in the repair and replication of DNA. Treatment with a single dose of UVB (100 mJ/cm<sup>2</sup>) upregulated IFNα and IFNβ in the skin of C57BL/6 mice. IFNα and IFNβ were predominantly produced by CD11b+ cells. In mice lacking the type I IFN receptor 1 (IFNAR1), the repair of CPD following cutaneous exposure to a single dose of UVB (100 mJ/cm<sup>2</sup>) was decreased. UVB induced the expression of the DNA repair gene xeroderma pigmentosum A (<i>XPA</i>) in wild-type (WT) mice. In contrast, such treatment in IFNAR1 (<i>IFNAR1-/-</i>) mice downregulated <i>XPA</i>. A local UVB regimen consisting of UVB radiation (150 mJ/cm<sup>2</sup>) for 4 days followed by sensitization with hapten 2,4, dinitrofluorobenzene (DNFB) resulted in significant suppression of immune responses in both WT and <i>IFNAR1-/-</i> mice. However, there were significantly higher CD4+CD25+Foxp3+ regulatory T-cells in the draining lymph nodes of <i>IFNAR1-/-</i> mice in comparison to WT mice. Overall, our studies reveal a previously unknown action of type I IFNs in the repair of photodamage and the prevention of UVB-induced immune suppression.https://www.mdpi.com/1422-0067/23/3/1822ultraviolet radiationtype I interferonsskinDNA repairimmune suppression |
| spellingShingle | Mohammad Asif Sherwani Israr Ahmad Monica J. Lewis Ahmed Abdelgawad Harunur Rashid Kevin Yang Ching-Yi Chen Chander Raman Craig A. Elmets Nabiha Yusuf Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune Suppression International Journal of Molecular Sciences ultraviolet radiation type I interferons skin DNA repair immune suppression |
| title | Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune Suppression |
| title_full | Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune Suppression |
| title_fullStr | Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune Suppression |
| title_full_unstemmed | Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune Suppression |
| title_short | Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune Suppression |
| title_sort | type i interferons enhance the repair of ultraviolet radiation induced dna damage and regulate cutaneous immune suppression |
| topic | ultraviolet radiation type I interferons skin DNA repair immune suppression |
| url | https://www.mdpi.com/1422-0067/23/3/1822 |
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