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

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• 作者：Takeshi Kawabe ; Nobu Suzuki ; Satoshi Yamaki ; Shu-lan Sun ; Atsuko Asao ; Yuko Okuyama ; Takanori So ; Yoichiro Iwakura and Naoto Ishii
• 关键词：Effector memory CD4+ T cells ; Mesenteric lymph nodes ; Small intestinal inflammation ; Th17 cells
• 刊名：European Journal of Immunology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：46
• 期：5
• 页码：1119-1131
• 全文大小：2022K
• ISSN：1521-4141

文摘

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 ₄β₇ integrin. Furthermore, MLN removal led to a significantly reduced number of peripheral ₄β₇⁺ 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.