布里格姆总医院的拉根研究所Douglas S. Kwon课题组的一项最新研究报道了CD8⁺ T细胞的免疫代谢缺陷破坏了HIV感染者肠道屏障的完整性。相关论文于2025年9月11日发表在《细胞》杂志上。

该研究组报道了PWH中结肠驻留CD8⁺ T细胞的免疫代谢缺陷导致肠上皮细胞凋亡和肠屏障完整性破坏的机制。该研究组发现，在PWH中，这些细胞下调脂质传感器过氧化物酶体增殖激活受体-γ (PPARγ)，导致细胞内脂滴减少，脂肪酸氧化受损，CD8⁺ T细胞从肠上皮细胞获取脂质，从而导致上皮细胞死亡。他们的研究结果表明，HIV相关的结肠CD8⁺ T细胞免疫代谢失调导致肠上皮稳态的丧失。这些结果确定了减少PWH和其他肠道屏障完整性破坏疾病合并症的潜在策略。

据悉，艾滋病毒感染的一个标志是，尽管接受了抗逆转录病毒治疗（ART），但艾滋病毒感染者（PWH）的肠道屏障完整性仍然受到破坏。这种破坏是艾滋病毒疾病进展的核心，但其主题仍然不完全清楚。

附：英文原文

Title: Immunometabolic defects of CD8+ T cells disrupt gut barrier integrity in people with HIV

Author: Upasana Das Adhikari, Leah M. Froehle, Alexandra N. Pipkin, Heeva Baharlou, Alice H. Linder, Palak Shah, Amanda Hussey, Qiming Zhang, Sarah Nyquist, Saleh Khwaled, Fangtao Chi, Swagata Goswami, Sabhyata Sedhain, Salina Hussain, Thomas J. Diefenbach, Benjamin J. Read, Byungji Kim, Darrell Irvine, Osaretin Asowata, Mark Ladinsky, Pamela Bjorkman, Fusi Madela, Shakeel Kader, Alex K. Shalek, Musie Ghebremichael, Henrik Kloverpris, Alison E. Ringel, mer H. Yilmaz, Douglas S. Kwon

Issue&Volume: 2025-09-11

Abstract: A hallmark of HIV infection is disruption of intestinal barrier integrity that persists in people with HIV (PWH) despite treatment with antiretroviral therapy (ART). This disruption is central to HIV disease progression, yet the causes remain incompletely understood. We report a mechanism by which immunometabolic defects in colon-resident CD8+ T cells in PWH lead to intestinal epithelial apoptosis and disruption of intestinal barrier integrity. We show that in PWH, these cells downregulate the lipid sensor peroxisome proliferator-activated receptor-γ (PPARγ), which results in reduced intracellular lipid droplets, impaired fatty acid oxidation, and acquisition of lipids by CD8+ T cells from intestinal epithelial cells, which then contributes to epithelial cell death. Our findings indicate that HIV-associated immunometabolic dysregulation of colon CD8+ T cells leads to loss of intestinal epithelial homeostasis. These results identify potential strategies to reduce comorbidities in PWH and other disorders with disrupted intestinal barrier integrity.

DOI: 10.1016/j.cell.2025.08.024

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00979-1