title: Central Role of Core Binding Factor β2 in Mucosa-Associated Lymphoid Tissue Organogenesis in Mouse.
abstract: Mucosa-associated lymphoid tissue (MALT) is a group of secondary and organized lymphoid tissue that develops at different mucosal surfaces. Peyer's patches (PPs), nasopharynx-associated lymphoid tissue (NALT), and tear duct-associated lymphoid tissue (TALT) are representative MALT in the small intestine, nasal cavity, and lacrimal sac, respectively. A recent study has shown that transcriptional regulators of core binding factor (Cbf) β2 and promotor-1-transcribed Runt-related transcription factor 1 (P1-Runx1) are required for the differentiation of CD3-CD4+CD45+ lymphoid tissue inducer (LTi) cells, which initiate and trigger the developmental program of PPs, but the involvement of this pathway in NALT and TALT development remains to be elucidated. Here we report that Cbfβ2 plays an essential role in NALT and TALT development by regulating LTi cell trafficking to the NALT and TALT anlagens. Cbfβ2 was expressed in LTi cells in all three types of MALT examined. Indeed, similar to the previous finding for PPs, we found that Cbfβ2-/- mice lacked NALT and TALT lymphoid structures. However, in contrast to PPs, NALT and TALT developed normally in the absence of P1-Runx1 or other Runx family members such as Runx2 and Runx3. LTi cells for NALT and TALT differentiated normally but did not accumulate in the respective lymphoid tissue anlagens in Cbfβ2-/- mice. These findings demonstrate that Cbfβ2 is a central regulator of the MALT developmental program, but the dependency of Runx proteins on the lymphoid tissue development would differ among PPs, NALT, and TALT.
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan; Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-asagi, Ibaraki-city, Osaka, 567-0085, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagatake
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan; Division of Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuyama
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Okura
authors.affiliation: Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Taniuchi
authors.affiliation: Department of Molecular Bone Biology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8588, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Ito
authors.affiliation: Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-asagi, Ibaraki-city, Osaka, 567-0085, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Shimojou
authors.affiliation: Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-asagi, Ibaraki-city, Osaka, 567-0085, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-asagi, Ibaraki-city, Osaka, 567-0085, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan; Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-asagi, Ibaraki-city, Osaka, 567-0085, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan; Department of Microbiology and Immunology, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Medical Genome Science, Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D050657:Core Binding Factor alpha Subunits / Q000235:genetics / Q000378:metabolism; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D009301:Nasolacrimal Duct / Q000378:metabolism / Q000473:pathology; D009305:Nasopharynx / Q000378:metabolism / Q000473:pathology; D038081:Organogenesis / Q000235:genetics*; D010581:Peyer's Patches / Q000378:metabolism* / Q000473:pathology
chemical_list: D050657:Core Binding Factor alpha Subunits; D050658:Core Binding Factor beta Subunit