Mitochondria maintain controlled activation state of epithelial-resident T lymphocytes

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Science Immunology  22 Jun 2018:
Vol. 3, Issue 24, eaan2543
DOI: 10.1126/sciimmunol.aan2543

Controlled activation

At the intestinal barrier, lymphocyte activation is a tightly regulated process that enables rapid responses to pathogens but avoids destructive inflammation. Konjar et al. examine how intraepithelial lymphocytes (IELs) maintain a controlled activation state, which is influenced by the composition of the mitochondrial membrane. Inflammation triggers changes in the mitochondrial membranes of IELs, particularly the cardiolipin composition, and these changes support rapid proliferation and effector functions. These findings reveal a role for mitochondria in controlling the activation state of IELs, thus furthering our insights into how mitochondria can influence immune responses.


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.

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