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

F Barone, S Nayar, J Campos, T Cloake, D R Withers, KM Toellner, Y Zhang, L Fouser, B Fisher, S Bowman, J Rangel-Moreno, Mde L Garcia-Hernandez, T D Randall, D Lucchesi, M Bombardieri, C Pitzalis, S A Luther, C D Buckley

Research output: Contribution to journalArticlepeer-review

162 Citations (Scopus)

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
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number35
DOIs
Publication statusPublished - 18 Aug 2015
Externally publishedYes

Keywords

  • IL-22
  • tertiary lymphoid organs
  • chemokines
  • Sjogren's syndrome
  • autoimmunity

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