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

Research output: Contribution to journalArticle

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Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology. / Nayar, Saba; Dias De Campos, Joana; Smith, Charlotte; Iannizzotto, Valentina; Gardner, David; 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; Buckley, Christopher; Coles, Mark C.; Barone, Francesca.

In: Proc. Natl. Acad. Sci. (USA), Vol. 116, No. 27, 201905301, 18.06.2019, p. 13490-13497.

Research output: Contribution to journalArticle

Harvard

Nayar, S, Dias De Campos, J, Smith, C, Iannizzotto, V, Gardner, D, Mourcin, F, Roulois, D, Turner, J, Sylvestre, M, Asam, S, Glaysher, B, Bowman, SJ, Fearon, DT, Filer, A, Tarte, K, Luther, SA, Fisher, B, Buckley, C, Coles, MC & Barone, F 2019, 'Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology', Proc. Natl. Acad. Sci. (USA), vol. 116, no. 27, 201905301, pp. 13490-13497. https://doi.org/10.1073/pnas.1905301116

APA

Nayar, S., Dias De Campos, J., Smith, C., Iannizzotto, V., Gardner, D., Mourcin, F., Roulois, D., Turner, J., Sylvestre, M., Asam, S., Glaysher, B., Bowman, S. J., Fearon, D. T., Filer, A., Tarte, K., Luther, S. A., Fisher, B., Buckley, C., Coles, M. C., & Barone, F. (2019). Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology. Proc. Natl. Acad. Sci. (USA), 116(27), 13490-13497. [201905301]. https://doi.org/10.1073/pnas.1905301116

Vancouver

Author

Nayar, Saba ; Dias De Campos, Joana ; Smith, Charlotte ; Iannizzotto, Valentina ; Gardner, David ; 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 ; Buckley, Christopher ; Coles, Mark C. ; Barone, Francesca. / Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology. In: Proc. Natl. Acad. Sci. (USA). 2019 ; Vol. 116, No. 27. pp. 13490-13497.

Bibtex

@article{905f64391f5440c1bda44da4bc17cd4f,
title = "Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology",
abstract = "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.",
keywords = "fibroblasts, Sj{\"o}gren{\textquoteright}s syndrome, autoimmunity, tertiary lymphoid structures",
author = "Saba Nayar and {Dias De Campos}, Joana and Charlotte Smith and Valentina Iannizzotto and David Gardner and Fr{\'e}d{\'e}ric Mourcin and David Roulois and Jason Turner and Marvin Sylvestre and Saba Asam and Bridget Glaysher and Bowman, {Simon J.} and Fearon, {Douglas T.} and Andrew Filer and Karin Tarte and Luther, {Sanjiv A.} and Benjamin Fisher and Christopher Buckley and Coles, {Mark C.} and Francesca Barone",
note = "Copyright {\textcopyright} 2019 the Author(s). Published by PNAS.",
year = "2019",
month = jun,
day = "18",
doi = "10.1073/pnas.1905301116",
language = "English",
volume = "116",
pages = "13490--13497",
journal = "Proc. Natl. Acad. Sci. (USA)",
number = "27",

}

RIS

TY - JOUR

T1 - Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology

AU - Nayar, Saba

AU - Dias De Campos, Joana

AU - Smith, Charlotte

AU - Iannizzotto, Valentina

AU - Gardner, David

AU - Mourcin, Frédéric

AU - Roulois, David

AU - Turner, Jason

AU - Sylvestre, Marvin

AU - Asam, Saba

AU - Glaysher, Bridget

AU - Bowman, Simon J.

AU - Fearon, Douglas T.

AU - Filer, Andrew

AU - Tarte, Karin

AU - Luther, Sanjiv A.

AU - Fisher, Benjamin

AU - Buckley, Christopher

AU - Coles, Mark C.

AU - Barone, Francesca

N1 - Copyright © 2019 the Author(s). Published by PNAS.

PY - 2019/6/18

Y1 - 2019/6/18

N2 - 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.

AB - 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.

KW - fibroblasts

KW - Sjögren’s syndrome

KW - autoimmunity

KW - tertiary lymphoid structures

UR - http://www.scopus.com/inward/record.url?scp=85068261921&partnerID=8YFLogxK

U2 - 10.1073/pnas.1905301116

DO - 10.1073/pnas.1905301116

M3 - Article

C2 - 31213547

VL - 116

SP - 13490

EP - 13497

JO - Proc. Natl. Acad. Sci. (USA)

JF - Proc. Natl. Acad. Sci. (USA)

IS - 27

M1 - 201905301

ER -