1. Cell Biology
  2. Immunology and Inflammation
Download icon

Identification of a super-functional Tfh-like subpopulation in murine lupus by pattern perception

  1. Stefanie Gryzik  Is a corresponding author
  2. Yen Hoang  Is a corresponding author
  3. Timo Lischke
  4. Elodie Mohr  Is a corresponding author
  5. Melanie Venzke
  6. Isabelle Kadner
  7. Josephine Poetzsch
  8. Detlef Groth
  9. Andreas Radbruch
  10. Andreas Hutloff
  11. Ria Baumgrass  Is a corresponding author
  1. German Rheumatism Research Center (DRFZ), Germany
  2. University of Potsdam, Germany
Research Article
  • Cited 0
  • Views 1,112
  • Annotations
Cite this article as: eLife 2020;9:e53226 doi: 10.7554/eLife.53226

Abstract

Dysregulated cytokine expression by T cells plays a pivotal role in the pathogenesis of autoimmune diseases. However, the identification of the corresponding pathogenic subpopulations is a challenge, since a distinction between physiological variation and a new quality in the expression of protein markers requires combinatorial evaluation. Here, we were able to identify a super-functional follicular helper T cell (Tfh)-like subpopulation in lupus-prone NZBxW mice with our binning approach "pattern recognition of immune cells (PRI)". PRI uncovered a subpopulation of IL-21+ IFN-ghigh PD-1low CD40Lhigh CXCR5- Bcl-6- T cells specifically expanded in diseased mice. In addition, these cells express high levels of TNF-a and IL-2, and provide B cell help for IgG production in an IL-21 and CD40L dependent manner. This super-functional T cell subset might be a superior driver of autoimmune processes due to a polyfunctional and high cytokine expression combined with Tfh-like properties.

Article and author information

Author details

  1. Stefanie Gryzik

    Signaltransduction, German Rheumatism Research Center (DRFZ), Berlin, Germany
    For correspondence
    s_gryzik@web.de
    Competing interests
    The authors declare that no competing interests exist.
  2. Yen Hoang

    Signaltransduction, German Rheumatism Research Center (DRFZ), Berlin, Germany
    For correspondence
    yen.hoang@drfz.de
    Competing interests
    The authors declare that no competing interests exist.
  3. Timo Lischke

    Signaltransduction, German Rheumatism Research Center (DRFZ), Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0413-4252
  4. Elodie Mohr

    Signaltransduction, German Rheumatism Research Center (DRFZ), Berlin, Germany
    For correspondence
    elodie.mohr@drfz.de
    Competing interests
    The authors declare that no competing interests exist.
  5. Melanie Venzke

    Signaltransduction, German Rheumatism Research Center (DRFZ), Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Isabelle Kadner

    Signaltransduction, German Rheumatism Research Center (DRFZ), Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Josephine Poetzsch

    Life Sciences, University of Potsdam, Potsdam, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Detlef Groth

    Bioinformatics, University of Potsdam, Potsdam, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Andreas Radbruch

    Cell Biology, German Rheumatism Research Center (DRFZ), Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Andreas Hutloff

    Chronic Immune Reactions, German Rheumatism Research Center (DRFZ), Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Ria Baumgrass

    Signaltransduction, German Rheumatism Research Center (DRFZ), Berlin, Germany
    For correspondence
    baumgrass@drfz.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3289-1608

Funding

Bundesministerium für Bildung und Forschung (0316164A)

  • Ria Baumgrass

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal experiments were approved by the local ethics committee LaGeSo (Landesamt für Gesundheit und Soziales) Berlin under animal experiment licenses T0187-01 and G0070/13.

Reviewing Editor

  1. Bernard Malissen, Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, France

Publication history

  1. Received: October 31, 2019
  2. Accepted: May 20, 2020
  3. Accepted Manuscript published: May 22, 2020 (version 1)
  4. Version of Record published: June 5, 2020 (version 2)

Copyright

© 2020, Gryzik et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,112
    Page views
  • 175
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Developmental Biology
    Nikhil R Bhagwat et al.
    Research Article Updated

    Protein modification by SUMO helps orchestrate the elaborate events of meiosis to faithfully produce haploid gametes. To date, only a handful of meiotic SUMO targets have been identified. Here, we delineate a multidimensional SUMO-modified meiotic proteome in budding yeast, identifying 2747 conjugation sites in 775 targets, and defining their relative levels and dynamics. Modified sites cluster in disordered regions and only a minority match consensus motifs. Target identities and modification dynamics imply that SUMOylation regulates all levels of chromosome organization and each step of meiotic prophase I. Execution-point analysis confirms these inferences, revealing functions for SUMO in S-phase, the initiation of recombination, chromosome synapsis and crossing over. K15-linked SUMO chains become prominent as chromosomes synapse and recombine, consistent with roles in these processes. SUMO also modifies ubiquitin, forming hybrid oligomers with potential to modulate ubiquitin signaling. We conclude that SUMO plays diverse and unanticipated roles in regulating meiotic chromosome metabolism.

    1. Cell Biology
    Mihaela Jagrić et al.
    Research Article Updated

    During metaphase, chromosome position at the spindle equator is regulated by the forces exerted by kinetochore microtubules and polar ejection forces. However, the role of forces arising from mechanical coupling of sister kinetochore fibers with bridging fibers in chromosome alignment is unknown. Here, we develop an optogenetic approach for acute removal of PRC1 to partially disassemble bridging fibers and show that they promote chromosome alignment. Tracking of the plus-end protein EB3 revealed longer antiparallel overlaps of bridging microtubules upon PRC1 removal, which was accompanied by misaligned and lagging kinetochores. Kif4A/kinesin-4 and Kif18A/kinesin-8 were found within the bridging fiber and largely lost upon PRC1 removal, suggesting that these proteins regulate the overlap length of bridging microtubules. We propose that PRC1-mediated crosslinking of bridging microtubules and recruitment of kinesins to the bridging fiber promote chromosome alignment by overlap length-dependent forces transmitted to the associated kinetochore fibers.