Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune Suppression.
Mohammad Asif SherwaniIsrar AhmadMonica J LewisAhmed S AbdelgawadHarunur RashidKevin YangChing-Yi ChenChander RamanCraig A ElmetsNabiha YusufPublished in: International journal of molecular sciences (2022)
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 2 ) 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 2 ) was decreased. UVB induced the expression of the DNA repair gene xeroderma pigmentosum A ( XPA ) in wild-type (WT) mice. In contrast, such treatment in IFNAR1 ( IFNAR1-/- ) mice downregulated XPA . A local UVB regimen consisting of UVB radiation (150 mJ/cm 2 ) for 4 days followed by sensitization with hapten 2,4, dinitrofluorobenzene (DNFB) resulted in significant suppression of immune responses in both WT and IFNAR1-/- mice. However, there were significantly higher CD4+CD25+Foxp3+ regulatory T-cells in the draining lymph nodes of IFNAR1-/- 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.
Keyphrases
- immune response
- wild type
- regulatory t cells
- high fat diet induced
- dendritic cells
- dna damage
- radiation induced
- dna repair
- skin cancer
- lymph node
- poor prognosis
- magnetic resonance
- oxidative stress
- endothelial cells
- computed tomography
- insulin resistance
- gene expression
- high glucose
- risk assessment
- radiation therapy
- adipose tissue
- climate change
- long non coding rna
- young adults
- early stage
- combination therapy
- toll like receptor
- single molecule
- human health
- wound healing
- smoking cessation
- quality improvement
- rectal cancer
- induced pluripotent stem cells
- adverse drug
- dna methylation