Author:
Barone Francesca,Nayar Saba,Campos Joana,Cloake Thomas,Withers David R.,Toellner Kai-Michael,Zhang Yang,Fouser Lynette,Fisher Benjamin,Bowman Simon,Rangel-Moreno Javier,Garcia-Hernandez Maria de la Luz,Randall Troy D.,Lucchesi Davide,Bombardieri Michele,Pitzalis Costantino,Luther Sanjiv A.,Buckley Christopher D.
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.
Publisher
Proceedings of the National Academy of Sciences
Cited by
158 articles.
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