Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune Suppression.
Type I Interferons Enhance the Repair of Ultraviolet Radiation-Induced DNA Damage and Regulate Cutaneous Immune Suppression.
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DOI：
10.3390/ijms23031822
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发表时间：
2022-02-05
影响因子：
5.6
通讯作者：
Yusuf N
中科院分区：
文献类型：
--
作者：
Sherwani MA;Ahmad I;Lewis MJ;Abdelgawad A;Rashid H;Yang K;Chen CY;Raman C;Elmets CA;Yusuf N
I型干扰素(IFN)是免疫反应的重要增强剂，在包括皮肤癌在内的人类癌症中表达下调。太阳紫外线(UV)B辐射是一种已被证实的环境致癌物质，其暴露导致皮肤癌的高发病率。紫外光的致癌作用可归因于环丁烷嘧啶二聚体(CPD)的形成以及DNA修复和复制的错误。单次中波紫外线(100mJ/cm~2)可上调C57BL/6小鼠皮肤干扰素α和干扰素β的表达。干扰素α和干扰素β主要由CD11b+细胞产生。在缺乏I型干扰素受体1(IFNAR1)的小鼠中，皮肤暴露于单剂量UVB(100mJ/cm2)后CPD的修复能力下降。UVB可诱导野生型(WT)小鼠DNA修复基因XPA的表达。相反，在IFNAR1(IFNAR1-/-)小鼠中，这种治疗下调了XPA的表达。局部UVB照射(150mJ/cm2)4d后用半抗原2，4，二硝基氟苯(DNFB)致敏，可显著抑制WT和IFNAR1-/-小鼠的免疫应答。然而，与WT小鼠相比，IFNAR1-/-小鼠引流淋巴结中的CD4+CD25+Foxp3+调节性T细胞显著增加。总体而言，我们的研究揭示了I型干扰素在修复光损伤和防止UVB诱导的免疫抑制中的未知作用。
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/cm2) 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/cm2) 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/cm2) 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.
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DOI：
10.1084/jem.170.4.1117
发表时间：
1989-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Applegate LA;Ley RD;Alcalay J;Kripke ML
通讯作者：
Kripke ML
影响因子：
5
作者：
Andersen, J.;VanScoy, S.;Reich, N. C.
通讯作者：
Reich, N. C.
DOI：
10.1093/jnci/53.5.1333
发表时间：
1974-01-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
KRIPKE, ML
通讯作者：
KRIPKE, ML
I型干扰素：正常皮肤中的关键参与者和选择皮肤恶性肿瘤。
影响因子：
1.5
作者：
Ismail A;Yusuf N
通讯作者：
Yusuf N
影响因子：
4.4
作者：
Loser, Karin;Apelt, Jenny;Beissert, Stefan
通讯作者：
Beissert, Stefan