Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice

Background: Peyer's patches (PPs) play a major role in mucosal immunity. However, their roles in nonsteroidal anti-inflammatory drug-induced enteropathy are poorly understood. Methods: Wild-type (WT) and PP-null mice were injected with indomethacin. Twenty-four hours later, the cellular profiles and cytokine levels in the PPs, mesenteric lymph nodes (MLNs), and lamina propria (LP) of the small intestine were measured. WT and PP-null mice were given antibiotics before indomethacin treatment to evaluate enteropathy. Naive CD4⁺ T cells were co-cultured with CD103⁺ or CD103^- dendritic cells (DCs) to analyze the interleukin (IL)-10 expression levels. Finally, WT mice adoptively transferred with CD103⁺ or CD103^- DCs were injected with indomethacin. Results: The proportion of CD103⁺ DCs in PPs and MLNs and IL-10-expressing CD4⁺ T cells of PPs and the LP increased after indomethacin treatment. The PP-null mice showed greater indomethacin-induced enteropathy, fewer CD103⁺ DCs in their MLNs, and lower proportion of IL-10-expressing CD4⁺ T cells of their LP than WT mice, regardless of commensal bacteria. Naive splenic CD4⁺ T cells co-cultured with CD103⁺ DCs isolated from the MLNs of indomethacin-injected WT mice produced a higher amount of IL-10 compared with those co-cultured with CD103^- DCs. Moreover, WT mice that received CD103⁺ DCs showed milder enteropathy than those that received CD103^- DCs. Conclusions: PPs play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy, and this protection is associated with an increase in CD103⁺ DCs and IL-10-producing CD4⁺ T cells in the intestine, independent of the commensal bacteria.