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Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology

Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional require...

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Autores principales: Nayar, Saba, Campos, Joana, Smith, Charlotte G., Iannizzotto, Valentina, Gardner, David H., Mourcin, Frédéric, Roulois, David, Turner, Jason, Sylvestre, Marvin, Asam, Saba, Glaysher, Bridget, Bowman, Simon J., Fearon, Douglas T., Filer, Andrew, Tarte, Karin, Luther, Sanjiv A., Fisher, Benjamin A., Buckley, Christopher D., Coles, Mark C., Barone, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613169/
https://www.ncbi.nlm.nih.gov/pubmed/31213547
http://dx.doi.org/10.1073/pnas.1905301116
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author Nayar, Saba
Campos, Joana
Smith, Charlotte G.
Iannizzotto, Valentina
Gardner, David H.
Mourcin, Frédéric
Roulois, David
Turner, Jason
Sylvestre, Marvin
Asam, Saba
Glaysher, Bridget
Bowman, Simon J.
Fearon, Douglas T.
Filer, Andrew
Tarte, Karin
Luther, Sanjiv A.
Fisher, Benjamin A.
Buckley, Christopher D.
Coles, Mark C.
Barone, Francesca
author_facet Nayar, Saba
Campos, Joana
Smith, Charlotte G.
Iannizzotto, Valentina
Gardner, David H.
Mourcin, Frédéric
Roulois, David
Turner, Jason
Sylvestre, Marvin
Asam, Saba
Glaysher, Bridget
Bowman, Simon J.
Fearon, Douglas T.
Filer, Andrew
Tarte, Karin
Luther, Sanjiv A.
Fisher, Benjamin A.
Buckley, Christopher D.
Coles, Mark C.
Barone, Francesca
author_sort Nayar, Saba
collection PubMed
description Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases.
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spelling pubmed-66131692019-07-15 Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology Nayar, Saba Campos, Joana Smith, Charlotte G. Iannizzotto, Valentina Gardner, David H. Mourcin, Frédéric Roulois, David Turner, Jason Sylvestre, Marvin Asam, Saba Glaysher, Bridget Bowman, Simon J. Fearon, Douglas T. Filer, Andrew Tarte, Karin Luther, Sanjiv A. Fisher, Benjamin A. Buckley, Christopher D. Coles, Mark C. Barone, Francesca Proc Natl Acad Sci U S A PNAS Plus Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases. National Academy of Sciences 2019-07-02 2019-06-18 /pmc/articles/PMC6613169/ /pubmed/31213547 http://dx.doi.org/10.1073/pnas.1905301116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Nayar, Saba
Campos, Joana
Smith, Charlotte G.
Iannizzotto, Valentina
Gardner, David H.
Mourcin, Frédéric
Roulois, David
Turner, Jason
Sylvestre, Marvin
Asam, Saba
Glaysher, Bridget
Bowman, Simon J.
Fearon, Douglas T.
Filer, Andrew
Tarte, Karin
Luther, Sanjiv A.
Fisher, Benjamin A.
Buckley, Christopher D.
Coles, Mark C.
Barone, Francesca
Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology
title Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology
title_full Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology
title_fullStr Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology
title_full_unstemmed Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology
title_short Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology
title_sort immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613169/
https://www.ncbi.nlm.nih.gov/pubmed/31213547
http://dx.doi.org/10.1073/pnas.1905301116
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