IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs

Francesca Barone; Saba Nayar; Joana Dias De Campos; David Withers; Kai-Michael Toellner; Benjamin Fisher; Simon Bowman; Thomas Cloake; Yang Zhang; Lynette Fouser; Javier Rangle-Moreno; Maria de la Luz Garcia-Hernandez; Troy D. Randall; Davide Lucchesi; Michele Bombardieri; Constantino Pitzalis; Christopher Buckley; Sanjev A. Luther

doi:10.1073/pnas.1503315112

IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs

Francesca Barone, Saba Nayar, Joana Dias De Campos, David Withers, Kai-Michael Toellner, Benjamin Fisher, Simon Bowman, Thomas Cloake, Yang Zhang, Lynette Fouser, Javier Rangle-Moreno, Maria de la Luz Garcia-Hernandez, Troy D. Randall, Davide Lucchesi, Michele Bombardieri, Constantino Pitzalis, Christopher Buckley, Sanjev A. Luther

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Abstract

The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22-blocking agents in B-cell-mediated autoimmune conditions.

Original language	English
Pages (from-to)	11024-11029
Number of pages	6
Journal	National Academy of Sciences. Proceedings
Volume	112
Issue number	35
DOIs	https://doi.org/10.1073/pnas.1503315112
Publication status	Published - 18 Aug 2015

Bibliographical note

Copyright & Usage: Freely available online through the PNAS open access option.

IL-22 regulates tertiary lymphoneogenesis, Francesca Barone et al, Proceedings of the National Academy of Sciences, Sep 2015, 112 (35) 11024-11029; DOI: 10.1073/pnas.1503315112

Keywords

IL-22
tertiary lymphoid organs
chemokines
Sjorgrens syndrome
autoimmunity

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BaroneF2015IL22
IL-22 regulates tertiary lymphoneogenesis, Francesca Barone et al, Proceedings of the National Academy of Sciences, Sep 2015, 112 (35) 11024-11029; DOI: 10.1073/pnas.1503315112
Final published version, 1.28 MBLicence: None: All rights reserved

Cite this

Barone, F., Nayar, S., Dias De Campos, J., Withers, D., Toellner, K-M., Fisher, B., Bowman, S., Cloake, T., Zhang, Y., Fouser, L., Rangle-Moreno, J., de la Luz Garcia-Hernandez, M., Randall, T. D., Lucchesi, D., Bombardieri, M., Pitzalis, C., Buckley, C., & Luther, S. A. (2015). IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs. National Academy of Sciences. Proceedings, 112(35), 11024-11029. https://doi.org/10.1073/pnas.1503315112

@article{16b73a8adc194d2080d7be9ebb7de6d9,

title = "IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs",

abstract = "The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22-blocking agents in B-cell-mediated autoimmune conditions. ",

keywords = "IL-22, tertiary lymphoid organs, chemokines, Sjorgrens syndrome, autoimmunity",

author = "Francesca Barone and Saba Nayar and {Dias De Campos}, Joana and David Withers and Kai-Michael Toellner and Benjamin Fisher and Simon Bowman and Thomas Cloake and Yang Zhang and Lynette Fouser and Javier Rangle-Moreno and {de la Luz Garcia-Hernandez}, Maria and Randall, {Troy D.} and Davide Lucchesi and Michele Bombardieri and Constantino Pitzalis and Christopher Buckley and Luther, {Sanjev A.}",

note = "Copyright & Usage: Freely available online through the PNAS open access option. IL-22 regulates tertiary lymphoneogenesis, Francesca Barone et al, Proceedings of the National Academy of Sciences, Sep 2015, 112 (35) 11024-11029; DOI: 10.1073/pnas.1503315112",

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doi = "10.1073/pnas.1503315112",

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Barone, F, Nayar, S, Dias De Campos, J, Withers, D , Toellner, K-M , Fisher, B, Bowman, S, Cloake, T, Zhang, Y, Fouser, L, Rangle-Moreno, J, de la Luz Garcia-Hernandez, M, Randall, TD, Lucchesi, D, Bombardieri, M, Pitzalis, C, Buckley, C & Luther, SA 2015, 'IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs', National Academy of Sciences. Proceedings, vol. 112, no. 35, pp. 11024-11029. https://doi.org/10.1073/pnas.1503315112

TY - JOUR

T1 - IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs

AU - Barone, Francesca

AU - Nayar, Saba

AU - Dias De Campos, Joana

AU - Withers, David

AU - Toellner, Kai-Michael

AU - Fisher, Benjamin

AU - Bowman, Simon

AU - Cloake, Thomas

AU - Zhang, Yang

AU - Fouser, Lynette

AU - Rangle-Moreno, Javier

AU - de la Luz Garcia-Hernandez, Maria

AU - Randall, Troy D.

AU - Lucchesi, Davide

AU - Bombardieri, Michele

AU - Pitzalis, Constantino

AU - Buckley, Christopher

AU - Luther, Sanjev A.

N1 - Copyright & Usage: Freely available online through the PNAS open access option. IL-22 regulates tertiary lymphoneogenesis, Francesca Barone et al, Proceedings of the National Academy of Sciences, Sep 2015, 112 (35) 11024-11029; DOI: 10.1073/pnas.1503315112

PY - 2015/8/18

Y1 - 2015/8/18

N2 - The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22-blocking agents in B-cell-mediated autoimmune conditions.

AB - The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22-blocking agents in B-cell-mediated autoimmune conditions.

KW - IL-22

KW - tertiary lymphoid organs

KW - chemokines

KW - Sjorgrens syndrome

KW - autoimmunity

U2 - 10.1073/pnas.1503315112

DO - 10.1073/pnas.1503315112

M3 - Article

SN - 1091-6490

VL - 112

SP - 11024

EP - 11029

JO - National Academy of Sciences. Proceedings

JF - National Academy of Sciences. Proceedings

IS - 35

ER -

IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs

Abstract

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Keywords

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