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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 publication

DOI

10.1073/pnas.1503315112

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

01/09/2015

Volume

112

Pages

11024 - 11029

Keywords

IL-22, Sjogren's syndrome, autoimmunity, chemokines, tertiary lymphoid organs, Animals, Autoantibodies, B-Lymphocytes, Chemokines, CXC, Interleukins, Lymphoid Tissue, Mice, Mice, Knockout