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

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.

Data availability

Flow cytometry data have been deposited in FlowRepository under the accession code FR-FCM-Z2C8. All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 1D, Figure 2A,B,D,E and figure supplement 1B; figure supplement 2B,E; figure supplement 3D, Figure 3C; figure supplement 1A-C, Figure 5A-D, Figure 6B,C and figure supplement 1A, Figure 7B+C

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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.

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  1. Stefanie Gryzik
  2. Yen Hoang
  3. Timo Lischke
  4. Elodie Mohr
  5. Melanie Venzke
  6. Isabelle Kadner
  7. Josephine Poetzsch
  8. Detlef Groth
  9. Andreas Radbruch
  10. Andreas Hutloff
  11. Ria Baumgrass
(2020)
Identification of a super-functional Tfh-like subpopulation in murine lupus by pattern perception
eLife 9:e53226.
https://doi.org/10.7554/eLife.53226

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