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

Academic Article

Abstract

  • © 2015, National Academy of Sciences. All rights reserved. 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.
  • Digital Object Identifier (doi)

    Author List

  • Barone F; Nayara S; Camposa J; Cloakea T; Withers DR; Toellner KM; Zhang Y; Fouser L; Fisher B; Bowman S
  • Start Page

  • 11024
  • End Page

  • 11029
  • Volume

  • 112
  • Issue

  • 35