Immunosuppression commonly disrupts the homeostasis of mutated normal skin, leading to widespread skin dysplasia and field cancerization. However, the immune system’s role in maintaining the normal state of mutated tissues remains uncertain. Herein, we demonstrate that T cell immunity to cutaneotropic papillomaviruses promotes the homeostasis of ultraviolet radiation-damaged skin. Mouse papillomavirus (MmuPV1) colonization blocks the expansion of mutant p53 clones in the epidermis in a CD8⁺ T cell-dependent manner. MmuPV1 activity is increased in p53-deficient keratinocytes, leading to their specific targeting by CD8⁺ T cells in the skin. Sun-exposed human skin containing mutant p53 clones shows increased epidermal beta-human papillomavirus (β-HPV) activity and CD8⁺ T cell infiltrates compared with sun-protected skin. The expansion of mutant p53 clones in premalignant skin lesions associates with β-HPV loss. Thus, immunity to commensal HPVs contributes to the homeostasis of mutated normal skin, highlighting the role of virome-immune system interactions in preserving aging human tissues.

中文翻译：

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共生瘤病毒免疫保留了高度突变的正常皮肤的稳态


免疫抑制通常会破坏突变正常皮肤的稳态，导致广泛的皮肤发育不良和野外癌变。然而，免疫系统在维持突变组织正常状态方面的作用仍不确定。在此，我们证明 T 细胞对嗜皮肤瘤病毒的免疫促进了紫外线辐射损伤皮肤的稳态。小鼠瘤病毒 （MmuPV1） 定植以 CD8 ⁺ T 细胞依赖性方式阻断突变 p53 克隆在表皮中的扩增。mmuPV1 活性在 p53 缺陷的角质形成细胞中增加，导致它们被皮肤中的 CD8⁺ T 细胞特异性靶向。与防晒皮肤相比，含有突变 p53 克隆的暴露在阳光下的人类皮肤显示表皮 β-人瘤病毒 （β-HPV） 活性和 CD8⁺ T 细胞浸润增加。突变 p53 克隆在癌前皮肤病变中的扩增与 β-HPV 丢失有关。因此，对共生 HPV 的免疫有助于突变的正常皮肤的稳态，突出了病毒组-免疫系统相互作用在保护衰老的人体组织方面的作用。