Ultraviolet radiation damages self noncoding RNA and is detected by TLR3.
Ultraviolet radiation damages self noncoding RNA and is detected by TLR3.
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暴露于来自太阳的紫外线B（UVB）辐射可导致晒伤、过早老化和致癌，但引起皮肤急性炎症的机制尚不清楚。在这里，我们表明，RNA释放从角质形成细胞UVB照射后，这刺激产生的炎症细胞因子肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6）从非辐射角质形成细胞和外周血单核细胞（PBMC）。全转录组测序显示，UVB照射角质形成细胞诱导的一些非编码RNA的双链结构域的改变。我们发现，这种UVB损伤的RNA是足以诱导细胞因子的生产从non-irradiated细胞，作为UVB照射的纯化的非编码RNA（U1 RNA）再现相同的反应，我们观察到UVB损伤的角质形成细胞。对UVB损伤的自身RNA和UVB损伤的角质形成细胞的反应依赖于Toll样受体3（TLR 3）和Toll样受体衔接分子1（TRIF）。作为对UVB暴露的反应，Tlr 3 −/−小鼠没有上调皮肤中的TNF-α。此外，TLR 3也是UVB辐射诱导的免疫抑制所必需的。这些研究结果表明，UVB损伤是由TLR 3检测的，而自身RNA是一种损伤相关的分子模式，可作为太阳损伤的内源性信号。
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.