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

Research output: Contribution to journalArticle

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.

Bibliographic 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

Details

Original languageEnglish
Pages (from-to)11024-11029
Number of pages6
JournalNational Academy of Sciences. Proceedings
Volume112
Issue number35
Early online date18 Aug 2015
Publication statusPublished - 1 Sep 2015

Keywords

  • IL-22, tertiary lymphoid organs, chemokines, Sjorgrens syndrome, autoimmunity