Abstract

Type I interferons (IFNs) are cytokines, that are important regulators of immune responses and are downregulated in human cancers, including skin cancer. Solar ultraviolet (UV) radiation is a proven environmental carcinogen, and exposure to solar radiation contributes to UVB induced immunosuppression. The formation of cyclobutane pyrimidine dimers (CPD) are a major cause of UVB induced immunosuppression. Our studies show that mice lacking the type I IFN receptor 1 (IFNAR1) had decreased repair of UVB induced CPD in the skin and increased immunosuppression. We hypothesize that type I IFNs will repair UVB induced DNA damage and prevent UVB induced immunosuppression in mice. To test our hypothesis, we will use mice, lacking IFNAR1, which is critical for signaling of type I IFNs; and XPA, that are deficient in the gene responsible for DNA repair. Using these unique mouse models, we will be able to (1) determine if regulatory T- cells develop in IFNAR1 knockout mice after exposure to UVB; and (2) evaluate whether regulation of UVB induced DNA damage by type I IFNs has any implications on immunosuppression in mice.

Public Health Relevance

Type I interferons (IFNs) are cytokines, that are important regulators of immune responses. Solar ultraviolet (UV) radiation is a proven environmental carcinogen, and exposure to solar radiation contributes to UVB induced immunosuppression. In this proposal, we will study the mechanism responsible for UVB induced immunosuppression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
3R01AR071157-03S1
Application #
9726663
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Cibotti, Ricardo
Project Start
2016-09-20
Project End
2021-08-31
Budget Start
2018-09-21
Budget End
2019-08-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Dermatology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Sherwani, Mohammad Asif; Tufail, Saba; Muzaffar, Anum Fatima et al. (2018) The skin microbiome and immune system: Potential target for chemoprevention? Photodermatol Photoimmunol Photomed 34:25-34
Sherwani, Mohammad Asif; Yang, Kevin; Jani, Aditi et al. (2018) Protective Effect of Baicalin Against TLR4-mediated UVA-induced Skin Inflammation. Photochem Photobiol :
Ergen, Elizabeth N; Yusuf, Nabiha (2018) Inhibition of interleukin-12 and/or interleukin-23 for the treatment of psoriasis: What is the evidence for an effect on malignancy? Exp Dermatol 27:737-747
Ahmad, Israr; Guroji, Purushotham; DeBrot, Amanda H et al. (2017) Loss of INK4a/Arf gene enhances ultraviolet radiation-induced cutaneous tumor development. Exp Dermatol 26:1018-1025