Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • Log in
The Journal of Immunology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Follow The Journal of Immunology on Twitter
  • Follow The Journal of Immunology on RSS

Interorganelle Tethering to Endocytic Organelles Determines Directional Cytokine Transport in CD4+ T Cells

Yan Zhou, Renping Zhao, Eva C. Schwarz, Rahmad Akbar, Mayis Kaba, Varsha Pattu, Volkhard Helms, Heiko Rieger, Paula Nunes-Hasler and Bin Qu
J Immunol December 1, 2020, 205 (11) 2988-3000; DOI: https://doi.org/10.4049/jimmunol.2000195
Yan Zhou
*Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421 Homburg, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Renping Zhao
*Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421 Homburg, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eva C. Schwarz
*Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421 Homburg, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Eva C. Schwarz
Rahmad Akbar
†Center for Bioinformatics, Saarland University, 66123 Saarbrücken, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rahmad Akbar
Mayis Kaba
‡Department of Cell Physiology and Metabolism, University Medical Center, University of Geneva, 1211 Geneva, Switzerland;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Varsha Pattu
§Department of Physiology, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421 Homburg, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Volkhard Helms
†Center for Bioinformatics, Saarland University, 66123 Saarbrücken, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Volkhard Helms
Heiko Rieger
¶Department of Theoretical Physics, Saarland University, 66123 Saarbrücken, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paula Nunes-Hasler
‡Department of Cell Physiology and Metabolism, University Medical Center, University of Geneva, 1211 Geneva, Switzerland;
‖Department of Pathology and Immunology, University Medical Center, University of Geneva, 1211 Geneva, Switzerland; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Paula Nunes-Hasler
Bin Qu
*Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421 Homburg, Germany;
#Leibniz Institute for New Materials, 66123 Saarbrücken, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Bin Qu
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF
Loading

Key Points

  • CytVs tether with lysosomes in T cells.

  • Lysosome-tethered CytVs are preferentially transported to their desired destination.

  • Lysosome tethering can mediate directionally distinctive CytV transport.

Abstract

Delivery of vesicles to their desired destinations plays a central role in maintaining proper cell functionality. In certain scenarios, depending on loaded cargos, the vesicles have spatially distinct destinations. For example, in T cells, some cytokines (e.g., IL-2) are polarized to the T cell–target cell interface, whereas the other cytokines are delivered multidirectionally (e.g., TNF-α). In this study, we show that in primary human CD4+ T cells, both TNF-α+ and IL-2+ vesicles can tether with endocytic organelles (lysosomes/late endosomes) by forming membrane contact sites. Tethered cytokine-containing vesicle (CytV)–endocytic organelle pairs are released sequentially. Only endocytic organelle-tethered CytVs are preferentially transported to their desired destination. Mathematical models suggest that endocytic organelle tethering could regulate the direction of cytokine transport by selectively attaching different microtubule motor proteins (such as kinesin and dynein) to the corresponding CytVs. These findings establish the previously unknown interorganelle tethering to endocytic organelles as a universal solution for directional cytokine transport in CD4+ T cells. Modulating tethering to endocytic organelles can, therefore, coordinately control directionally distinct cytokine transport.

Footnotes

  • This work was funded by the Deutsche Forschungsgemeinschaft (Projects SFB1027 A2 [to B.Q.], SFB1027 A3 [to H.R.], and SFB1027 C3 [to V.H.]) and by the Leibniz Association (INM Fellow to B.Q.). P.N.-H. is supported by the Novartis Foundation (Grant 17B078), the Prof. Dr. Max Cloëtta Foundation 2019 Medical Researcher Award, and the Swiss National Science Foundation (Grant 310030_189094).

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article:

    CLEM
    correlative light and electron microscopy
    co-IP
    coimmunoprecipitation
    CytV
    cytokine-containing vesicle
    dist
    distal area
    EM
    electron microscopy
    ER
    endoplasmic reticulum
    F
    forward
    IS
    immunological synapse
    LCSM
    laser confocal scanning microscopy
    LG
    lytic granule
    MCS
    membrane contact site
    MTOC
    microtubule organizing center
    N.A.
    numerical aperture
    PDB
    Protein Data Bank
    R
    reverse
    SIM
    structured illumination microscopy
    siRNA
    small interfering RNA
    SNARE
    soluble NSF attachment protein receptor
    TIRF
    total internal reflection fluorescence
    WT
    wild-type.

  • Received February 20, 2020.
  • Accepted September 20, 2020.
  • Copyright © 2020 by The American Association of Immunologists, Inc.
View Full Text

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$37.50

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

Log in using your username and password

Forgot your user name or password?
PreviousNext
Back to top

In this issue

The Journal of Immunology: 205 (11)
The Journal of Immunology
Vol. 205, Issue 11
1 Dec 2020
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Immunology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Interorganelle Tethering to Endocytic Organelles Determines Directional Cytokine Transport in CD4+ T Cells
(Your Name) has forwarded a page to you from The Journal of Immunology
(Your Name) thought you would like to see this page from the The Journal of Immunology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Interorganelle Tethering to Endocytic Organelles Determines Directional Cytokine Transport in CD4+ T Cells
Yan Zhou, Renping Zhao, Eva C. Schwarz, Rahmad Akbar, Mayis Kaba, Varsha Pattu, Volkhard Helms, Heiko Rieger, Paula Nunes-Hasler, Bin Qu
The Journal of Immunology December 1, 2020, 205 (11) 2988-3000; DOI: 10.4049/jimmunol.2000195

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Interorganelle Tethering to Endocytic Organelles Determines Directional Cytokine Transport in CD4+ T Cells
Yan Zhou, Renping Zhao, Eva C. Schwarz, Rahmad Akbar, Mayis Kaba, Varsha Pattu, Volkhard Helms, Heiko Rieger, Paula Nunes-Hasler, Bin Qu
The Journal of Immunology December 1, 2020, 205 (11) 2988-3000; DOI: 10.4049/jimmunol.2000195
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosures
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • The miR-23a∼27a∼24-2 microRNA Cluster Promotes Inflammatory Polarization of Macrophages
  • Cbl-b Is Upregulated and Plays a Negative Role in Activated Human NK Cells
  • IL-17A–Secreting Memory γδ T Cells Play a Pivotal Role in Sensitization and Development of Hypersensitivity Pneumonitis
Show more IMMUNE REGULATION

Similar Articles

Navigate

  • Home
  • Current Issue
  • Next in The JI
  • Archive
  • Brief Reviews
  • Pillars of Immunology
  • Translating Immunology

For Authors

  • Submit a Manuscript
  • Instructions for Authors
  • About the Journal
  • Journal Policies
  • Editors

General Information

  • Advertisers
  • Subscribers
  • Rights and Permissions
  • Accessibility Statement
  • Public Access
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2021 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606