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.
Significance Ectopic clusters of immune cells that mimic the structure and function of secondary lymphoid organs are defined as tertiary lymphoid organs (TLOs). They have been observed at sites of chronic inflammation for decades, but their formation and function have remained enigmatic. TLOs are thought to contribute to disease pathogenesis by promoting autoreactive lymphocyte survival and autoantibody production. In this study we identify a novel role for the cytokine IL-22 in TLO development and biology. We provide evidence that IL-22 expression within TLOs is instrumental for the production of the lymphoid chemokines, chemokine (C-X-C motif) ligand 13 and chemokine (C-X-C motif) ligand 12, which in turn orchestrate B-cell clustering, lymphoid aggregation, and autoantibody production. Our data provide a strong rationale for targeting IL-22 in TLO-associated autoimmune diseases.