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

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

Proceedings of the National Academy of Sciences of the United States of America (2015-08-20)
Francesca Barone, Saba Nayar, Joana Campos, Thomas Cloake, David R Withers, Kai-Michael Toellner, Yang Zhang, Lynette Fouser, Benjamin Fisher, Simon Bowman, Javier Rangel-Moreno, Maria de la Luz Garcia-Hernandez, Troy D Randall, Davide Lucchesi, Michele Bombardieri, Costantino Pitzalis, Sanjiv A Luther, Christopher D Buckley
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.

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