TY - JOUR
T1 - Mitochondria maintain controlled activation state of epithelial-resident T lymphocytes
AU - Konjar, Špela
AU - Frising, Ulrika C.
AU - Ferreira, Cristina
AU - Hinterleitner, Reinhard
AU - Mayassi, Toufic
AU - Zhang, Qifeng
AU - Blankenhaus, Birte
AU - Haberman, Nejc
AU - Loo, Yunhua
AU - Guedes, Joana
AU - Baptista, Marta
AU - Innocentin, Silvia
AU - Stange, Joerg
AU - Strathdee, Douglas
AU - Jabri, Bana
AU - Veldhoen, Marc
N1 - Publisher Copyright:
Copyright © 2018 The Authors, some rights reserved.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85052645995&partnerID=8YFLogxK
U2 - 10.1126/sciimmunol.aan2543
DO - 10.1126/sciimmunol.aan2543
M3 - Article
C2 - 29934344
AN - SCOPUS:85052645995
SN - 2470-9468
VL - 3
JO - Science immunology
JF - Science immunology
IS - 24
M1 - eaan2543
ER -