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  Mitochondrial Priming by CD28

Geltink, R. I. K., O’Sullivan, D., Corrado, M., Bremser, A., Buck, M. D., Buescher, J. M., et al. (2017). Mitochondrial Priming by CD28. Cell, 171, 385-397. doi:10.1016/j.immuni.2017.03.022.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-8575-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-C3E2-F
Genre: Journal Article

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Klein Geltink et al..pdf (Publisher version), 6MB
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 Creators:
Geltink, Ramon I. Klein1, Author
O’Sullivan, David1, Author
Corrado, Mauro1, Author
Bremser, Anna1, Author
Buck, Michael D.1, Author
Buescher, Joerg M.1, Author
Firat, Elke2, Author
Zhu, Xuekai2, Author
Niedermann, Gabriele2, Author
Caputa, George1, Author
Kelly, Beth1, Author
Warthorst, Ursula2, Author
Rensing-Ehl, Anne2, Author
Kyle, Ryan L.1, Author
Vandersarren, Lana2, Author
Curtis, Jonathan D.1, Author
Patterson, Annette E.1, Author
Lawless, Simon1, Author
Grzes, Katarzyna1, Author
Qiu, Jing1, Author
Sanin, David E.1, AuthorKretz, Oliver2, AuthorHuber, Tobias B.2, AuthorJanssens, Sophie2, AuthorLambrecht, Bart N.2, AuthorRambold, Angelika1, Author              Pearce, Edward J.1, Author              Pearce, Erika L.1, Author               more..
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
2External Organizations, ou_persistent22              

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 Abstract: T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand. Early CD28-dependent mitochondrial engagement is needed for T cells to remodel cristae, develop SRC, and rapidly produce cytokines upon restimulation—cardinal features of protective memory T cells. Our data show that initial CD28 signals during T cell activation prime mitochondria with latent metabolic capacity that is essential for future T cell responses.

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Language(s): eng - English
 Dates: 2017-10-05
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.immuni.2017.03.022
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Title: Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 171 Sequence Number: - Start / End Page: 385 - 397 Identifier: ISSN: 0092-8674
CoNE: https://pure.mpg.de/cone/journals/resource/954925463183