Show simple item record

dc.contributor.authorKiritsy, Michael C
dc.contributor.authorMcCann, Katelyn J
dc.contributor.authorMott, Daniel
dc.contributor.authorHolland, Steven M
dc.contributor.authorBehar, Samuel M
dc.contributor.authorSassetti, Christopher M
dc.contributor.authorOlive, Andrew J
dc.date.accessioned2023-03-14T20:03:27Z
dc.date.available2023-03-14T20:03:27Z
dc.date.issued2021-11-02
dc.identifier.citationKiritsy MC, McCann K, Mott D, Holland SM, Behar SM, Sassetti CM, Olive AJ. Mitochondrial respiration contributes to the interferon gamma response in antigen-presenting cells. Elife. 2021 Nov 2;10:e65109. doi: 10.7554/eLife.65109. PMID: 34726598; PMCID: PMC8598164.en_US
dc.identifier.eissn2050-084X
dc.identifier.doi10.7554/eLife.65109en_US
dc.identifier.pmid34726598
dc.identifier.urihttp://hdl.handle.net/20.500.14038/51813
dc.description.abstractThe immunological synapse allows antigen-presenting cells (APCs) to convey a wide array of functionally distinct signals to T cells, which ultimately shape the immune response. The relative effect of stimulatory and inhibitory signals is influenced by the activation state of the APC, which is determined by an interplay between signal transduction and metabolic pathways. While pathways downstream of toll-like receptors rely on glycolytic metabolism for the proper expression of inflammatory mediators, little is known about the metabolic dependencies of other critical signals such as interferon gamma (IFNγ). Using CRISPR-Cas9, we performed a series of genome-wide knockout screens in murine macrophages to identify the regulators of IFNγ-inducible T cell stimulatory or inhibitory proteins MHCII, CD40, and PD-L1. Our multiscreen approach enabled us to identify novel pathways that preferentially control functionally distinct proteins. Further integration of these screening data implicated complex I of the mitochondrial respiratory chain in the expression of all three markers, and by extension the IFNγ signaling pathway. We report that the IFNγ response requires mitochondrial respiration, and APCs are unable to activate T cells upon genetic or chemical inhibition of complex I. These findings suggest a dichotomous metabolic dependency between IFNγ and toll-like receptor signaling, implicating mitochondrial function as a fulcrum of innate immunity.en_US
dc.language.isoenen_US
dc.relationThis article is based on a previously available preprint in bioRxiv, https://doi.org/10.1101/2020.11.22.393538.
dc.relation.ispartofeLifeen_US
dc.relation.urlhttps://doi.org/10.7554/elife.65109en_US
dc.rightsThis is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.; CC0 1.0 Universalen_US
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectAPC functionen_US
dc.subjectIFN gammaen_US
dc.subjectPD-L1 regulationen_US
dc.subjectcomplex Ien_US
dc.subjecthumanen_US
dc.subjectimmunologyen_US
dc.subjectimmunometabolismen_US
dc.subjectinflammationen_US
dc.subjectmitochondrial respirationen_US
dc.subjectmouseen_US
dc.titleMitochondrial respiration contributes to the interferon gamma response in antigen-presenting cellsen_US
dc.typeJournal Articleen_US
dc.source.journaltitleeLife
dc.source.volume10
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland
dc.identifier.journaleLife
refterms.dateFOA2023-03-14T20:03:28Z
dc.contributor.departmentMicrobiology and Physiological Systemsen_US
dc.contributor.departmentMorningside Graduate School of Biomedical Sciencesen_US
dc.contributor.departmentT.H. Chan School of Medicine
dc.description.thesisprogramMD/PhD


Files in this item

Thumbnail
Name:
elife-65109-v2.pdf
Size:
6.760Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.; CC0 1.0 Universal
Except where otherwise noted, this item's license is described as This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.; CC0 1.0 Universal