共生乳头瘤病毒免疫保护高度突变的正常皮肤的稳态

IF 48.8 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2024-12-12 DOI:10.1016/j.ccell.2024.11.013

Heehwa G. Son, Dat Thinh Ha, Yun Xia, Tiancheng Li, Jasmine Blandin, Tomonori Oka, Marjan Azin, Danielle N. Conrad, Can Zhou, Yuhan Zeng, Tatsuya Hasegawa, John D. Strickley, Jonathan L. Messerschmidt, Ranya Guennoun, Tal H. Erlich, Gregory L. Shoemaker, Luke H. Johnson, Kenneth E. Palmer, David E. Fisher, Thomas D. Horn, Shadmehr Demehri

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引用次数: 0

摘要

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区癌变。然而，免疫系统在维持突变组织正常状态中的作用仍不确定。在此，我们证明了T细胞对嗜皮性乳头瘤病毒的免疫促进了紫外线辐射损伤皮肤的稳态。小鼠乳头瘤病毒（MmuPV1）定植以CD8+ T细胞依赖的方式阻止突变p53克隆在表皮中的扩增。在p53缺失的角质形成细胞中，MmuPV1活性增加，导致它们被皮肤中的CD8+ T细胞特异性靶向。与受阳光照射的皮肤相比，含有突变p53克隆的暴露于阳光下的皮肤显示表皮β-人乳头瘤病毒（β-HPV）活性和CD8+ T细胞浸润增加。突变型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的免疫有助于突变正常皮肤的稳态，突出了病毒-免疫系统相互作用在保存衰老人体组织中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Commensal papillomavirus immunity preserves the homeostasis of highly mutated normal skin

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Commensal papillomavirus immunity preserves the homeostasis of highly mutated normal skin

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.

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来源期刊

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.