Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, Lisbon, 1649-028, Portugal.
Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
Sci Immunol. 2018 Jun 22;3(24). doi: 10.1126/sciimmunol.aan2543.
Epithelial-resident T lymphocytes, such as intraepithelial lymphocytes (IELs) located at the intestinal barrier, can offer swift protection against invading pathogens. Lymphocyte activation is strictly regulated because of its potential harmful nature and metabolic cost, and most lymphocytes are maintained in a quiescent state. However, IELs are kept in a heightened state of activation resembling effector T cells but without cytokine production or clonal proliferation. We show that this controlled activation state correlates with alterations in the IEL mitochondrial membrane, especially the cardiolipin composition. Upon inflammation, the cardiolipin composition is altered to support IEL proliferation and effector function. Furthermore, we show that cardiolipin makeup can particularly restrict swift IEL proliferation and effector functions, reducing microbial containment capability. These findings uncover an alternative mechanism to control cellular activity, special to epithelial-resident T cells, and a novel role for mitochondria, maintaining cells in a metabolically poised state while enabling rapid progression to full functionality.
上皮组织驻留 T 淋巴细胞，如位于肠道屏障的上皮内淋巴细胞 (IEL)，可以迅速提供针对入侵病原体的保护。由于淋巴细胞激活具有潜在的危害性和代谢成本，因此其激活受到严格调控，大多数淋巴细胞处于静止状态。然而，IEL 保持着类似于效应 T 细胞的高度激活状态，但不产生细胞因子或克隆增殖。我们发现这种受控的激活状态与 IEL 线粒体膜的改变，特别是心磷脂组成有关。在炎症时，心磷脂组成发生改变以支持 IEL 的增殖和效应功能。此外，我们发现心磷脂组成可以特别限制 IEL 的迅速增殖和效应功能，从而降低微生物控制能力。这些发现揭示了一种控制细胞活性的替代机制，这是上皮组织驻留 T 细胞所特有的，以及线粒体的新作用，使细胞保持在代谢平衡状态，同时能够迅速发挥全部功能。
