Mitochondria maintain controlled activation state of epithelial-resident T lymphocytes

Špela Konjar, Ulrika C. Frising, Cristina Ferreira, Reinhard Hinterleitner, Toufic Mayassi, Qifeng Zhang, Birte Blankenhaus, Nejc Haberman, Yunhua Loo, Joana Guedes, Marta Baptista, Silvia Innocentin, Joerg Stange, Douglas Strathdee, Bana Jabri, Marc Veldhoen

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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.

Original languageEnglish
Article numbereaan2543
JournalScience immunology
Volume3
Issue number24
DOIs
StatePublished - 2018
Externally publishedYes

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