Nat Med：紫外线照射诱导非编码RNA改变导致皮肤急性炎症

暴露在来自太阳的紫外线B（UVB）辐射下会导致皮肤晒伤，过早衰老和癌变，但紫外线B引发的皮肤急性炎症的机制还不是很清楚。

近日，Nature Medicine杂志上的一则研究表明紫外线照射引发的RNA变化由角质细胞释放带来的，这一效应刺激未接受照射的角质细胞和外周血单个核细胞（PBMCs）中炎性细胞因子肿瘤坏死因子α（TNF-α）及白细胞介素-6（IL-6）产生。

全转录组测序结果显示，紫外线辐射角质细胞后诱导一些非编码RNA双链域发生改变。研究人员发现，这种紫外线损伤的RNA足以引起未照射细胞细胞因子的生产，这些细胞因子作为一种纯化的非编码RNA在接受紫外线照射后会产生相同的应答。

紫外线损伤的自身RNA和紫外线损伤的角质细胞取决于Toll样受体3（TLR3）以及Toll样受体适配器分子1（TRIF）。TLR3敲除小鼠在紫外线照射下，皮肤中的TNF-α没有上调。此外，TLR3对紫外线辐射引起的免疫抑制也是必要的。结果证明UVB的危害与TLR3有关，自身RNA是紫外照射的内源性损伤信号。

Ultraviolet radiation damages self noncoding RNA and is detected by TLR3.

Bernard JJ, Cowing-Zitron C, Nakatsuji T, Muehleisen B, Muto J, Borkowski AW, Martinez L, Greidinger EL, Yu BD, Gallo RL.

Exposure to ultraviolet B (UVB) radiation from the sun can result in sunburn, premature aging and carcinogenesis, but the mechanism responsible for acute inflammation of the skin is not well understood. Here we show that RNA is released from keratinocytes after UVB exposure and that this stimulates production of the inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) from nonirradiated keratinocytes and peripheral blood mononuclear cells (PBMCs). Whole-transcriptome sequencing revealed that UVB irradiation of keratinocytes induced alterations in the double-stranded domains of some noncoding RNAs. We found that this UVB-damaged RNA was sufficient to induce cytokine production from nonirradiated cells, as UVB irradiation of a purified noncoding RNA (U1 RNA) reproduced the same response as the one we observed to UVB-damaged keratinocytes. The responses to both UVB-damaged self-RNAs and UVB-damaged keratinocytes were dependent on Toll-like receptor 3 (TLR3) and Toll-like receptor adaptor molecule 1 (TRIF). In response to UVB exposure, Tlr3(-/-) mice did not upregulate TNF-α in the skin. Moreover, TLR3 was also necessary for UVB-radiation-induced immune suppression. These findings establish that UVB damage is detected by TLR3 and that self-RNA is a damage-associated molecular pattern that serves as an endogenous signal of solar injury.