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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109 Citations (Scopus)
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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 languageEnglish
Pages (from-to)11024-11029
Number of pages6
JournalNational Academy of Sciences. Proceedings
Volume112
Issue number35
DOIs
Publication statusPublished - 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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