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Tertiary Lymphoid Structures: Diversity in Their Development, Composition, and Role

Catarina Gago da Graça, Lisa G. M. van Baarsen and Reina E. Mebius
J Immunol January 15, 2021, 206 (2) 273-281; DOI: https://doi.org/10.4049/jimmunol.2000873
Catarina Gago da Graça
*Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit, 1081HZ Amsterdam, the Netherlands;
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Lisa G. M. van Baarsen
†Department of Rheumatology and Clinical Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands;
‡Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, University of Amsterdam, the Netherlands; and
§Amsterdam Rheumatology and Immunology Center, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands
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Reina E. Mebius
*Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit, 1081HZ Amsterdam, the Netherlands;
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Abstract

Lymph node stromal cells coordinate the adaptive immune response in secondary lymphoid organs, providing both a structural matrix and soluble factors that regulate survival and migration of immune cells, ultimately promoting Ag encounter. In several inflamed tissues, resident fibroblasts can acquire lymphoid-stroma properties and drive the formation of ectopic aggregates of immune cells, named tertiary lymphoid structures (TLSs). Mature TLSs are functional sites for the development of adaptive responses and, consequently, when present, can have an impact in both autoimmunity and cancer conditions. In this review, we go over recent findings concerning both lymph node stromal cells and TLSs function and formation and further describe what is currently known about their role in disease, particularly their potential in tolerance.

Footnotes

  • This work was supported by Netherlands Organisation for Health Research and Development (NWO ZonMw) TOP Grant 91217014 (to R.E.M. and L.G.M.v.B).

  • Abbreviations used in this article:

    CP
    cryptopatch
    DC
    dendritic cell
    FDC
    follicular dendritic cell
    FRC
    fibroblastic reticular cell
    GC
    germinal center
    HEV
    high endothelial venule
    iBALT
    induced BALT
    ILF
    isolated lymphoid follicle
    LEC
    lymphatic endothelial cell
    LN
    lymph node
    LNSC
    LN stromal cell
    LS
    lymphoid structure
    LT
    lymphotoxin
    LTi
    lymphoid tissue inducer
    LTβR
    LT-β receptor
    MRC
    marginal reticular cell
    Pdpn
    podoplanin
    RA
    rheumatoid arthritis
    SLO
    secondary lymphoid organ
    TLS
    tertiary lymphoid structure
    TRA
    tissue-restricted Ag
    Treg
    T regulatory cell.

  • Received July 24, 2020.
  • Accepted November 3, 2020.
  • Copyright © 2021 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 206 (2)
The Journal of Immunology
Vol. 206, Issue 2
15 Jan 2021
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Tertiary Lymphoid Structures: Diversity in Their Development, Composition, and Role
Catarina Gago da Graça, Lisa G. M. van Baarsen, Reina E. Mebius
The Journal of Immunology January 15, 2021, 206 (2) 273-281; DOI: 10.4049/jimmunol.2000873

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Tertiary Lymphoid Structures: Diversity in Their Development, Composition, and Role
Catarina Gago da Graça, Lisa G. M. van Baarsen, Reina E. Mebius
The Journal of Immunology January 15, 2021, 206 (2) 273-281; DOI: 10.4049/jimmunol.2000873
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