IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs.
Barone F., Nayar S., Campos J., Cloake T., Withers DR., Toellner K-M., Zhang Y., Fouser L., Fisher B., Bowman S., Rangel-Moreno J., Garcia-Hernandez MDLL., Randall TD., Lucchesi D., Bombardieri M., Pitzalis C., Luther SA., Buckley CD.
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.