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  • 1
    Publication Date: 2011-01-06
    Description: CD4(+) T regulatory cells (T(regs)), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, T(regs) were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota, particularly clusters IV and XIVa of the genus Clostridium, promoted T(reg) cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor-beta and affected Foxp3(+) T(reg) number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969237/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969237/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Atarashi, Koji -- Tanoue, Takeshi -- Shima, Tatsuichiro -- Imaoka, Akemi -- Kuwahara, Tomomi -- Momose, Yoshika -- Cheng, Genhong -- Yamasaki, Sho -- Saito, Takashi -- Ohba, Yusuke -- Taniguchi, Tadatsugu -- Takeda, Kiyoshi -- Hori, Shohei -- Ivanov, Ivaylo I -- Umesaki, Yoshinori -- Itoh, Kikuji -- Honda, Kenya -- R00 DK085329/DK/NIDDK NIH HHS/ -- R01 AI052359/AI/NIAID NIH HHS/ -- R01 AI056154/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2011 Jan 21;331(6015):337-41. doi: 10.1126/science.1198469. Epub 2010 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21205640" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/pharmacology ; Cecum/microbiology ; Cells, Cultured ; Clostridium/growth & development/*immunology ; Colitis/immunology/pathology/prevention & control ; Colon/*immunology/metabolism/*microbiology ; Feces/microbiology ; Forkhead Transcription Factors/metabolism ; Germ-Free Life ; Immunity, Innate ; Immunoglobulin E/biosynthesis ; Interleukin-10/immunology/metabolism ; Intestinal Mucosa/*immunology/metabolism ; Intestine, Small/immunology ; Metagenome ; Mice ; Mice, Inbred A ; Mice, Inbred BALB C ; Receptors, Pattern Recognition/physiology ; Specific Pathogen-Free Organisms ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Regulatory/*immunology/metabolism ; Transforming Growth Factor beta/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-11-15
    Description: Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Furusawa, Yukihiro -- Obata, Yuuki -- Fukuda, Shinji -- Endo, Takaho A -- Nakato, Gaku -- Takahashi, Daisuke -- Nakanishi, Yumiko -- Uetake, Chikako -- Kato, Keiko -- Kato, Tamotsu -- Takahashi, Masumi -- Fukuda, Noriko N -- Murakami, Shinnosuke -- Miyauchi, Eiji -- Hino, Shingo -- Atarashi, Koji -- Onawa, Satoshi -- Fujimura, Yumiko -- Lockett, Trevor -- Clarke, Julie M -- Topping, David L -- Tomita, Masaru -- Hori, Shohei -- Ohara, Osamu -- Morita, Tatsuya -- Koseki, Haruhiko -- Kikuchi, Jun -- Honda, Kenya -- Hase, Koji -- Ohno, Hiroshi -- England -- Nature. 2013 Dec 19;504(7480):446-50. doi: 10.1038/nature12721. Epub 2013 Nov 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa 230-0045, Japan [2] The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan [3]. ; 1] RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa 230-0045, Japan [2] The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan [3] Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan [4]. ; 1] RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa 230-0045, Japan [2] Institute for Advanced Biosciences, Keio University, Yamagata 997-0052, Japan [3]. ; RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa 230-0045, Japan. ; Institute for Advanced Biosciences, Keio University, Yamagata 997-0052, Japan. ; 1] RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa 230-0045, Japan [2] Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan. ; Faculty of Agriculture, Shizuoka University, Shizuoka 422-8529, Japan. ; 1] RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa 230-0045, Japan [2] PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan. ; The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. ; Preventative Health National Research Flagship, CSIRO Food and Nutritional Sciences, South Australia 5000, Australia. ; 1] RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa 230-0045, Japan [2] Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan [3] Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan. ; 1] Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan [2] RIKEN Center for Sustainable Resource Science, Kanagawa 230-0045, Japan. ; 1] RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa 230-0045, Japan [2] CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan. ; 1] RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa 230-0045, Japan [2] The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan [3] PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan [4].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24226770" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation/drug effects ; Adoptive Transfer ; Animals ; Butyrates/analysis/*metabolism/pharmacology ; *Cell Differentiation/drug effects ; Colitis/drug therapy/pathology ; Colon/cytology/*immunology/metabolism/*microbiology ; Conserved Sequence ; Female ; *Fermentation ; Forkhead Transcription Factors/genetics ; Germ-Free Life ; Histones/metabolism ; Homeostasis/drug effects ; Intestinal Mucosa/cytology/immunology ; Lymphocyte Count ; Magnetic Resonance Spectroscopy ; Male ; Metabolome ; Mice ; Promoter Regions, Genetic/drug effects ; *Symbiosis ; T-Lymphocytes, Regulatory/*cytology/drug effects/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-03-29
    Description: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉FANTOM Consortium and the RIKEN PMI and CLST (DGT) -- Forrest, Alistair R R -- Kawaji, Hideya -- Rehli, Michael -- Baillie, J Kenneth -- de Hoon, Michiel J L -- Haberle, Vanja -- Lassmann, Timo -- Kulakovskiy, Ivan V -- Lizio, Marina -- Itoh, Masayoshi -- Andersson, Robin -- Mungall, Christopher J -- Meehan, Terrence F -- Schmeier, Sebastian -- Bertin, Nicolas -- Jorgensen, Mette -- Dimont, Emmanuel -- Arner, Erik -- Schmidl, Christian -- Schaefer, Ulf -- Medvedeva, Yulia A -- Plessy, Charles -- Vitezic, Morana -- Severin, Jessica -- Semple, Colin A -- Ishizu, Yuri -- Young, Robert S -- Francescatto, Margherita -- Alam, Intikhab -- Albanese, Davide -- Altschuler, Gabriel M -- Arakawa, Takahiro -- Archer, John A C -- Arner, Peter -- Babina, Magda -- Rennie, Sarah -- Balwierz, Piotr J -- Beckhouse, Anthony G -- Pradhan-Bhatt, Swati -- Blake, Judith A -- Blumenthal, Antje -- Bodega, Beatrice -- Bonetti, Alessandro -- Briggs, James -- Brombacher, Frank -- Burroughs, A Maxwell -- Califano, Andrea -- Cannistraci, Carlo V -- Carbajo, Daniel -- Chen, Yun -- Chierici, Marco -- Ciani, Yari -- Clevers, Hans C -- Dalla, Emiliano -- Davis, Carrie A -- Detmar, Michael -- Diehl, Alexander D -- Dohi, Taeko -- Drablos, Finn -- Edge, Albert S B -- Edinger, Matthias -- Ekwall, Karl -- Endoh, Mitsuhiro -- Enomoto, Hideki -- Fagiolini, Michela -- Fairbairn, Lynsey -- Fang, Hai -- Farach-Carson, Mary C -- Faulkner, Geoffrey J -- Favorov, Alexander V -- Fisher, Malcolm E -- Frith, Martin C -- Fujita, Rie -- Fukuda, Shiro -- Furlanello, Cesare -- Furino, Masaaki -- Furusawa, Jun-ichi -- Geijtenbeek, Teunis B -- Gibson, Andrew P -- Gingeras, Thomas -- Goldowitz, Daniel -- Gough, Julian -- Guhl, Sven -- Guler, Reto -- Gustincich, Stefano -- Ha, Thomas J -- Hamaguchi, Masahide -- Hara, Mitsuko -- Harbers, Matthias -- Harshbarger, Jayson -- Hasegawa, Akira -- Hasegawa, Yuki -- Hashimoto, Takehiro -- Herlyn, Meenhard -- Hitchens, Kelly J -- Ho Sui, Shannan J -- Hofmann, Oliver M -- Hoof, Ilka -- Hori, Furni -- Huminiecki, Lukasz -- Iida, Kei -- Ikawa, Tomokatsu -- Jankovic, Boris R -- Jia, Hui -- Joshi, Anagha -- Jurman, Giuseppe -- Kaczkowski, Bogumil -- Kai, Chieko -- Kaida, Kaoru -- Kaiho, Ai -- Kajiyama, Kazuhiro -- Kanamori-Katayama, Mutsumi -- Kasianov, Artem S -- Kasukawa, Takeya -- Katayama, Shintaro -- Kato, Sachi -- Kawaguchi, Shuji -- Kawamoto, Hiroshi -- Kawamura, Yuki I -- Kawashima, Tsugumi -- Kempfle, Judith S -- Kenna, Tony J -- Kere, Juha -- Khachigian, Levon M -- Kitamura, Toshio -- Klinken, S Peter -- Knox, Alan J -- Kojima, Miki -- Kojima, Soichi -- Kondo, Naoto -- Koseki, Haruhiko -- Koyasu, Shigeo -- Krampitz, Sarah -- Kubosaki, Atsutaka -- Kwon, Andrew T -- Laros, Jeroen F J -- Lee, Weonju -- Lennartsson, Andreas -- Li, Kang -- Lilje, Berit -- Lipovich, Leonard -- Mackay-Sim, Alan -- Manabe, Ri-ichiroh -- Mar, Jessica C -- Marchand, Benoit -- Mathelier, Anthony -- Mejhert, Niklas -- Meynert, Alison -- Mizuno, Yosuke -- de Lima Morais, David A -- Morikawa, Hiromasa -- Morimoto, Mitsuru -- Moro, Kazuyo -- Motakis, Efthymios -- Motohashi, Hozumi -- Mummery, Christine L -- Murata, Mitsuyoshi -- Nagao-Sato, Sayaka -- Nakachi, Yutaka -- Nakahara, Fumio -- Nakamura, Toshiyuki -- Nakamura, Yukio -- Nakazato, Kenichi -- van Nimwegen, Erik -- Ninomiya, Noriko -- Nishiyori, Hiromi -- Noma, Shohei -- Noazaki, Tadasuke -- Ogishima, Soichi -- Ohkura, Naganari -- Ohimiya, Hiroko -- Ohno, Hiroshi -- Ohshima, Mitsuhiro -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry A -- Pain, Arnab -- Passier, Robert -- Patrikakis, Margaret -- Persson, Helena -- Piazza, Silvano -- Prendergast, James G D -- Rackham, Owen J L -- Ramilowski, Jordan A -- Rashid, Mamoon -- Ravasi, Timothy -- Rizzu, Patrizia -- Roncador, Marco -- Roy, Sugata -- Rye, Morten B -- Saijyo, Eri -- Sajantila, Antti -- Saka, Akiko -- Sakaguchi, Shimon -- Sakai, Mizuho -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schneider, Claudio -- Schultes, Erik A -- Schulze-Tanzil, Gundula G -- Schwegmann, Anita -- Sengstag, Thierry -- Sheng, Guojun -- Shimoji, Hisashi -- Shimoni, Yishai -- Shin, Jay W -- Simon, Christophe -- Sugiyama, Daisuke -- Sugiyama, Takaai -- Suzuki, Masanori -- Suzuki, Naoko -- Swoboda, Rolf K -- 't Hoen, Peter A C -- Tagami, Michihira -- Takahashi, Naoko -- Takai, Jun -- Tanaka, Hiroshi -- Tatsukawa, Hideki -- Tatum, Zuotian -- Thompson, Mark -- Toyodo, Hiroo -- Toyoda, Tetsuro -- Valen, Elvind -- van de Wetering, Marc -- van den Berg, Linda M -- Verado, Roberto -- Vijayan, Dipti -- Vorontsov, Ilya E -- Wasserman, Wyeth W -- Watanabe, Shoko -- Wells, Christine A -- Winteringham, Louise N -- Wolvetang, Ernst -- Wood, Emily J -- Yamaguchi, Yoko -- Yamamoto, Masayuki -- Yoneda, Misako -- Yonekura, Yohei -- Yoshida, Shigehiro -- Zabierowski, Susan E -- Zhang, Peter G -- Zhao, Xiaobei -- Zucchelli, Silvia -- Summers, Kim M -- Suzuki, Harukazu -- Daub, Carsten O -- Kawai, Jun -- Heutink, Peter -- Hide, Winston -- Freeman, Tom C -- Lenhard, Boris -- Bajic, Vladimir B -- Taylor, Martin S -- Makeev, Vsevolod J -- Sandelin, Albin -- Hume, David A -- Carninci, Piero -- Hayashizaki, Yoshihide -- BB/F003722/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G022771/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I001107/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- R01 GM084875/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):462-70. doi: 10.1038/nature13182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Conserved Sequence/genetics ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Genes, Essential/genetics ; Genome/genetics ; Humans ; Mice ; *Molecular Sequence Annotation ; Open Reading Frames/genetics ; Organ Specificity ; Promoter Regions, Genetic/*genetics ; RNA, Messenger/analysis/genetics ; Transcription Factors/metabolism ; Transcription Initiation Site ; Transcription, Genetic/genetics ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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