title: Mesenteric lymph nodes contribute to proinflammatory Th17-cell generation during inflammation of the small intestine in mice.
abstract: 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 α4 β7 integrin. Furthermore, MLN removal led to a significantly reduced number of peripheral α4 β7 (+) 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.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawabe
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Nobu
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaki
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Sun
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Asao
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okuyama
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: So
authors.affiliation: Division of Experimental Animal Immunology, Research Institute for Biological Sciences, Tokyo University of Science, Chiba, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Ishii
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004751:Enteritis / Q000276:immunology*; D007156:Immunologic Memory; D007249:Inflammation / Q000473:pathology; D016023:Integrins / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology*; D008643:Mesentery / Q000276:immunology*; D051379:Mice; D010581:Peyer's Patches / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016023:Integrins; C071777:integrin alpha4beta7
keywords: Effector memory CD4+ T cells; Mesenteric lymph nodes; Small intestinal inflammation; Th17 cells