美国马萨诸塞州总医院和哈佛医学院Shadmehr Demehri团队近期取得重要工作进展,他们研究提出,共生乳头瘤病毒免疫保护高度突变的正常皮肤的稳态。相关研究成果2024年12月12日在线发表于《癌细胞》杂志上。
据介绍,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局部癌变。然而,免疫系统在维持突变组织正常状态方面的作用仍然不确定。
研究人员证明T细胞对促皮乳头瘤病毒的免疫,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,阻断表皮中突变p53克隆的扩增。MmuPV1活性在p53缺陷的角质形成细胞中增加,导致其被皮肤中的CD8+ T细胞特异性靶向。
与防晒皮肤相比,暴露在阳光下的含有突变p53克隆的人皮肤显示出,表皮β-人乳头瘤病毒(β-HPV)活性和CD8+ T细胞浸润的增加。突变型p53克隆在癌前皮肤病变中的扩增与β-HPV的缺失有关。
因此,对共生HPV的免疫力有助于突变正常皮肤的稳态,突显了病毒-免疫系统相互作用在保护衰老人体组织中的作用。
附:英文原文
Title: Commensal papillomavirus immunity preserves the homeostasis of highly mutated normal skin
Author: 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, Victor A. Neel, Rosalynn M. Nazarian, Joongho J. Joh, Shadmehr Demehri
Issue&Volume: 2024-12-12
Abstract: 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.
DOI: 10.1016/j.ccell.2024.11.013
Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00448-3
Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:38.585
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx