Chronic Stress Induces Colonic Tertiary Lymphoid Organ Formation and Protection Against Secondary Injury Through IL-23/IL-22 Signaling.

Significance Here, we demonstrate that chronic stress induces the formation of tertiary lymphoid organs (TLOs) in the colon of a mouse model of Crohn’s disease (CD)-like ileitis. Stress induces increased production of interleukin-23 (IL-23) and IL-22, which subsequently increases TLO formation and production of antimicrobial peptides. Interestingly, chronic stress is also protective against chemically induced colitis. While previous studies have linked stress and glucocorticoids to constituents of the TLO formation pathway, our study shows that stress directly increases TLO formation. Furthermore, stress is canonically associated with more severe inflammation. However, not all patients who experience stress have worse disease. Therefore, this study has translational significance because it demonstrates a condition where stress has a beneficial effect.