Mesenteric lymph nodes contribute to proinflammatory Th17-cell generation during inflammation of the small intestine in mice

T cells of the small intestine, including Th17 cells, are critically involved in host protection from microbial infection, and also contribute to the pathogenesis of small bowel inflammatory disorders. Accumulating evidence suggests that mesenteric lymph nodes (MLNs) play important roles in gut-tropic T-cell generation, although it is still unclear if MLNs are involved in the pathogenesis of small intestine inflammation. To address this issue, we analyzed the roles of both MLNs and Peyer's patches (PPs) by evaluating MLN- or PP-deficient mice in an experimental model of small intestine inflammation, induced by CD3-specific mAb injection. Interestingly, MLNs, but not PPs, were essential for the pathogenesis of intestinal inflammation, in particular the accumulation and infiltration of CD4⁺ T-cell populations, including Th17 cells, from the blood. In addition, CD4⁺ T-cell accumulation was dependent on the function of the α₄β₇ integrin. Furthermore, MLN removal led to a significantly reduced number of peripheral α₄β₇⁺ CD4⁺ effector memory T cells under normal conditions, suggesting that MLNs may play a role in maintaining the number of gut-tropic CD4⁺ effector memory T cells circulating in the blood. Taken together, the present study highlights the important role of MLNs in contributing to the pathogenesis of small intestine inflammation.