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Revisiting Current Concepts on the Tolerogenicity of Steady-State Dendritic Cell Subsets and Their Maturation Stages

Manfred B. Lutz, Ronald A. Backer and Björn E. Clausen
J Immunol April 15, 2021, 206 (8) 1681-1689; DOI: https://doi.org/10.4049/jimmunol.2001315
Manfred B. Lutz
*Institute for Virology and Immunobiology, University of Würzburg, 97070 Würzburg, Germany; and
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Ronald A. Backer
†Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55122 Mainz, Germany
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Björn E. Clausen
†Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55122 Mainz, Germany
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Abstract

The original concept stated that immature dendritic cells (DC) act tolerogenically whereas mature DC behave strictly immunogenically. Meanwhile, it is also accepted that phenotypically mature stages of all conventional DC subsets can promote tolerance as steady-state migratory DC by transporting self-antigens to lymph nodes to exert unique functions on regulatory T cells. We propose that in vivo 1) there is little evidence for a tolerogenic function of immature DC during steady state such as CD4 T cell anergy induction, 2) all tolerance as steady-state migratory DC undergo common as well as subset-specific molecular changes, and 3) these changes differ by quantitative and qualitative markers from immunogenic DC, which allows one to clearly distinguish tolerogenic from immunogenic migratory DC.

Footnotes

  • This work was supported by the Deutsche Forschungsgemeinschaft through grants to M.B.L. (LU851/14-1), to R.A.B. (BA5939/2-1), and to B.E.C. (CL419/2-1, CL419/4-1 and CRC-1292) and the Interdisciplinary Center for Clinical Research Würzburg (A-408). B.E.C. and R.A.B. are members of the Research Center for Immunotherapy Mainz. All authors equally contributed to the conceptualization and writing of this article.

  • Abbreviations used in this article:

    BM
    bone marrow
    DC
    dendritic cell
    inf-migDC
    immunogenic migratory DC
    LC
    Langerhans cell
    LN
    lymph node
    MHC I
    MHC class I
    MHC II
    MHC class II
    migDC
    migratory DC
    pDC
    plasmacytoid DC
    pTreg
    peripheral Treg
    RA
    retinoic acid
    resDC
    DC functioning as resident sensor
    SP
    spleen
    TNF-BMDC
    TNF-matured bone marrow–derived DC
    tolDC
    tolerogenic DC
    tol-migDC
    tolerogenic migratory DC
    Treg
    regulatory T cell
    tTreg
    thymic CD4+Foxp3+ Treg.

  • Received November 22, 2020.
  • Accepted January 11, 2021.
  • Copyright © 2021 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 206 (8)
The Journal of Immunology
Vol. 206, Issue 8
15 Apr 2021
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Revisiting Current Concepts on the Tolerogenicity of Steady-State Dendritic Cell Subsets and Their Maturation Stages
Manfred B. Lutz, Ronald A. Backer, Björn E. Clausen
The Journal of Immunology April 15, 2021, 206 (8) 1681-1689; DOI: 10.4049/jimmunol.2001315

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Revisiting Current Concepts on the Tolerogenicity of Steady-State Dendritic Cell Subsets and Their Maturation Stages
Manfred B. Lutz, Ronald A. Backer, Björn E. Clausen
The Journal of Immunology April 15, 2021, 206 (8) 1681-1689; DOI: 10.4049/jimmunol.2001315
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