Papers - Honda, Kenya

IL-10 produced by macrophages regulates epithelial integrity in the small intestine

Morhardt T., Hayashi A., Ochi T., Quirós M., Kitamoto S., Nagao-Kitamoto H., Kuffa P., Atarashi K., Honda K., Kao J., Nusrat A., Kamada N.

Scientific Reports (Scientific Reports)  9 ( 1 )  2019.12

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© 2019, The Author(s). Macrophages (Mϕs) are known to be major producers of the anti-inflammatory cytokine interleukin-10 (IL-10) in the intestine, thus playing an important role in maintaining gastrointestinal homeostasis. Mϕs that reside in the small intestine (SI) have been previously shown to be regulated by dietary antigens, while colonic Mϕs are regulated by the microbiota. However, the role which resident Mϕs play in SI homeostasis has not yet been fully elucidated. Here, we show that SI Mϕs regulate the integrity of the epithelial barrier via secretion of IL-10. We used an animal model of non-steroidal anti-inflammatory drug (NSAID)-induced SI epithelial injury to show that IL-10 is mainly produced by MHCII+ CD64+ Ly6Clow Mϕs early in injury and that it is involved in the restoration of the epithelial barrier. We found that a lack of IL-10, particularly its secretion by Mϕs, compromised the recovery of SI epithelial barrier. IL-10 production by MHCII+ CD64+ Ly6Clow Mϕs in the SI is not regulated by the gut microbiota, hence depletion of the microbiota did not influence epithelial regeneration in the SI. Collectively, these results highlight the critical role IL-10-producing Mϕs play in recovery from intestinal epithelial injury induced by NSAID.

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Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis

Nakamoto N., Sasaki N., Aoki R., Miyamoto K., Suda W., Teratani T., Suzuki T., Koda Y., Chu P., Taniki N., Yamaguchi A., Kanamori M., Kamada N., Hattori M., Ashida H., Sakamoto M., Atarashi K., Narushima S., Yoshimura A., Honda K., Sato T., Kanai T.

Nature Microbiology (Nature Microbiology)  4 ( 3 ) 492 - 503 2019.03

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© 2019, The Author(s), under exclusive licence to Springer Nature Limited. Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease and its frequent complication with ulcerative colitis highlights the pathogenic role of epithelial barrier dysfunction. Intestinal barrier dysfunction has been implicated in the pathogenesis of PSC, yet its underlying mechanism remains unknown. Here, we identify Klebsiella pneumonia in the microbiota of patients with PSC and demonstrate that K. pneumoniae disrupts the epithelial barrier to initiate bacterial translocation and liver inflammatory responses. Gnotobiotic mice inoculated with PSC-derived microbiota exhibited T helper 17 (T H 17) cell responses in the liver and increased susceptibility to hepatobiliary injuries. Bacterial culture of mesenteric lymph nodes in these mice isolated K. pneumoniae, Proteus mirabilis and Enterococcus gallinarum, which were prevalently detected in patients with PSC. A bacterial-organoid co-culture system visualized the epithelial-damaging effect of PSC-derived K. pneumoniae that was associated with bacterial translocation and susceptibility to T H 17-mediated hepatobiliary injuries. We also show that antibiotic treatment ameliorated the T H 17 immune response induced by PSC-derived microbiota. These results highlight the role of pathobionts in intestinal barrier dysfunction and liver inflammation, providing insights into therapeutic strategies for PSC.

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A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

Tanoue T., Morita S., Plichta D., Skelly A., Suda W., Sugiura Y., Narushima S., Vlamakis H., Motoo I., Sugita K., Shiota A., Takeshita K., Yasuma-Mitobe K., Riethmacher D., Kaisho T., Norman J., Mucida D., Suematsu M., Yaguchi T., Bucci V., Inoue T., Kawakami Y., Olle B., Roberts B., Hattori M., Xavier R., Atarashi K., Honda K.

Nature (Nature)  565 ( 7741 ) 600 - 605 2019.01

ISSN  00280836

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© 2019, Springer Nature Limited. There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103 + dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.

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Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis

Ladinsky M., Araujo L., Zhang X., Veltri J., Galan-Diez M., Soualhi S., Lee C., Irie K., Pinker E., Narushima S., Bandyopadhyay S., Nagayama M., Elhenawy W., Coombes B., Ferraris R., Honda K., Iliev I., Gao N., Bjorkman P., Ivanov I.

Science (Science)  363 ( 6431 )  2019

ISSN  00368075

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2017 © The Authors. Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall–associated proteins, including an antigen that stimulates mucosal T helper 17 (T H 17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)–dependent manner. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB and decreased epithelial antigen acquisition, with consequent loss of mucosal T H 17 cells. Our findings demonstrate direct communication between a resident gut microbe and the host and show that under physiological conditions, IECs acquire antigens from commensal bacteria for generation of T cell responses to the resident microbiota.

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Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid

Morita H., Kubo T., Rückert B., Ravindran A., Soyka M., Rinaldi A., Sugita K., Wawrzyniak M., Wawrzyniak P., Motomura K., Tamari M., Orimo K., Okada N., Arae K., Saito K., Altunbulakli C., Castro-Giner F., Tan G., Neumann A., Sudo K., O'Mahony L., Honda K., Nakae S., Saito H., Mjösberg J., Nilsson G., Matsumoto K., Akdis M., Akdis C.

Journal of Allergy and Clinical Immunology (Journal of Allergy and Clinical Immunology)   2019

ISSN  00916749

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© 2019 American Academy of Allergy, Asthma & Immunology Background: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus clarification of the mechanisms that underlie regulation of ILC2 activation has received significant attention. Although innate lymphoid cells are divided into 3 major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T cells have not been well characterized. Objective: We sought to determine the factors that induce regulatory innate lymphoid cells (ILCregs). Methods: IL-10 + ILCregs induced from ILC2s by using retinoic acid (RA) were analyzed with RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissue from healthy subjects and patients with chronic rhinosinusitis with nasal polyps and lung tissue from house dust mite– or saline-treated mice. Results: RA induced IL-10 secretion by human ILC2s but not type 2 cytokines. IL-10 + ILCregs, which were converted from ILC2s by means of RA stimulation, expressed a regulatory T cell–like signature with expression of IL-10, cytotoxic T lymphocyte–associated protein 4, and CD25, with downregulated effector type 2–related markers, such as chemoattractant receptor–homologous molecule on T H 2 cells and ST2, and suppressed activation of CD4 + T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy subjects or lung tissue from saline-treated mice, but numbers were increased in nasal tissue from patients with chronic rhinosinusitis with nasal polyps and in lung tissue from house dust mite–treated mice. Enzymes for RA synthesis were upregulated in airway epithelial cells during type 2 inflammation in vivo and by IL-13 in vitro. Conclusion: We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs.

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Mining the microbiota for microbial and metabolite-based immunotherapies

Skelly A., Sato Y., Kearney S., Honda K.

Nature Reviews Immunology (Nature Reviews Immunology)   2019

ISSN  14741733

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© 2019, The Author(s), under exclusive licence to Springer Nature Limited. Trillions of microorganisms transit through and reside in the mammalian gastrointestinal tract each day, collectively producing thousands of small molecules and metabolites with local and systemic effects on host physiology. Identifying effector microorganisms that causally affect host phenotype and deciphering the underlying mechanisms have become foci of microbiome research and have begun to enable the development of microbiota-based therapeutics. Two complementary, reductionist approaches have commonly been used: the first starts with an immune phenotype and narrows down the microbiota to identify responsible effector bacteria, while the second starts with bacteria-derived molecules and metabolites and seeks to understand their effects on the host immune system. Together, these strategies provide the basis for the rational design of microbial and metabolite-based therapeutics that target and ameliorate immune deficits in patients.

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Computer-guided design of optimal microbial consortia for immune system modulation

Stein R., Tanoue T., Szabady R., Bhattarai S., Olle B., Norman J., Suda W., Oshima K., Hattori M., Gerber G., Sander C., Honda K., Bucci V.

eLife (eLife)  7 2018.04

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© Stein et al. Manipulation of the gut microbiota holds great promise for the treatment of diseases. However, a major challenge is the identification of therapeutically potent microbial consortia that colonize the host effectively while maximizing immunologic outcome. Here, we propose a novel workflow to select optimal immune-inducing consortia from microbiome compositicon and immune effectors measurements. Using published and newly generated microbial and regulatory T-cell (T reg ) data from germ-free mice, we estimate the contributions of twelve Clostridia strains with known immune-modulating effect to T reg induction. Combining this with a longitudinal data-constrained ecological model, we predict the ability of every attainable and ecologically stable subconsortium in promoting T reg activation and rank them by the T reg Induction Score (TrIS). Experimental validation of selected consortia indicates a strong and statistically significant correlation between predicted TrIS and measured T reg . We argue that computational indexes, such as the TrIS, are valuable tools for the systematic selection of immune-modulating bacteriotherapeutics.

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Clarithromycin expands CD11b⁺Gr-1⁺cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia

Namkoong H., Ishii M., Fujii H., Yagi K., Asami T., Asakura T., Suzuki S., Hegab A., Kamata H., Tasaka S., Atarashi K., Nakamoto N., Iwata S., Honda K., Kanai T., Hasegawa N., Koyasu S., Betsuyaku T.

PLoS Pathogens (PLoS Pathogens)  14 ( 4 )  2018.04

ISSN  15537366

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© 2018 Namkoong et al. Macrolides are used to treat various inflammatory diseases owing to their immunomodulatory properties; however, little is known about their precise mechanism of action. In this study, we investigated the functional significance of the expansion of myeloid-derived suppressor cell (MDSC)-like CD11b+Gr-1+cells in response to the macrolide antibiotic clarithromycin (CAM) in mouse models of shock and post-influenza pneumococcal pneumonia as well as in humans. Intraperitoneal administration of CAM markedly expanded splenic and lung CD11b+Gr-1+cell populations in naïve mice. Notably, CAM pretreatment enhanced survival in a mouse model of lipopolysaccharide (LPS)-induced shock. In addition, adoptive transfer of CAM-treated CD11b+Gr-1+cells protected mice against LPS-induced lethality via increased IL-10 expression. CAM also improved survival in post-influenza, CAM-resistant pneumococcal pneumonia, with improved lung pathology as well as decreased interferon (IFN)-γ and increased IL-10 levels. Adoptive transfer of CAM-treated CD11b+Gr-1+cells protected mice from post-influenza pneumococcal pneumonia. Further analysis revealed that the CAM-induced CD11b+Gr-1+cell expansion was dependent on STAT3-mediated Bv8 production and may be facilitated by the presence of gut commensal microbiota. Lastly, an analysis of peripheral blood obtained from healthy volunteers following oral CAM administration showed a trend toward the expansion of human MDSC-like cells (Lineage−HLA-DR−CD11b+CD33+) with increased arginase 1 mRNA expression. Thus, CAM promoted the expansion of a unique population of immunosuppressive CD11b+Gr-1+cells essential for the immunomodulatory properties of macrolides.

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Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure

Kamo, Takehiro, Akazawa, Hiroshi, Suda, Wataru, Saga-Kamo, Akiko, Shimizu, Yu, Yagi, Hiroki, Liu, Qing, Nomura, Seitaro, Naito, Atsuhiko T., Takeda, Norifumi, Harada, Mutsuo, Toko, Haruhiro, Kumagai, Hidetoshi, Ikeda, Yuichi, Takimoto, Eiki, Suzuki, Jun-ichi, Honda, Kenya, Morita, Hidetoshi, Hattori, Masahira, Komuro, Issei

PLOS ONE 12 ( 3 )  2017.03

Research paper (scientific journal),  ISSN  1932-6203

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Microbiota Diumal Rhythmicity Programs Host Transcriptome Oscillations

Thaiss, Christoph A., Levy, Maayan, Korem, Tal, Dohnalova, Lenka, Shapiro, Hagit, Jaitin, Diego A., David, Eyal, Winter, Deborah R., Gury-BenAri, Meital, Tatirovsky, Evgeny, Tuganbaev, Timur, Federici, Sara, Zmora, Niv, Zeevi, David, Dori-Bachash, Mally, Pevsner-Fischer, Meirav, Kartvelishvily, Elena, Brandis, Alexander, Harmelin, Alon, Shibolet, Oren, Halpern, Zamir, Honda, Kenya, Amit, Ido, Segal, Eran, Elinav, Eran

CELL 167 ( 6 ) 1495 - + 2016.12

Research paper (scientific journal),  ISSN  0092-8674

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Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut

Kakihana, Kazuhiko, Fujioka, Yuki, Suda, Wataru, Najima, Yuho, Kuwata, Go, Sasajima, Satoshi, Mimura, Iyo, Morita, Hidetoshi, Sugiyama, Daisuke, Nishikawa, Hiroyoshi, Hattori, Masahira, Hino, Yutaro, Ikegawa, Shuntaro, Yamamoto, Keita, Toya, Takashi, Doki, Noriko, Koizumi, Koichi, Honda, Kenya, Ohashi, Kazuteru

BLOOD 128 ( 16 ) 2083 - 2088 2016.10

Research paper (scientific journal),  ISSN  0006-4971

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A subpopulation of high IL-21-producing CD4(+) T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers (vol 6, 30784, 2016)

Jones, Leigh, Ho, Wen Qi, Ying, Sze, Ramakrishna, Lakshmi, Srinivasan, Kandhadayar G., Yurieva, Marina, Ng, Wan Pei, Subramaniam, Sharrada, Hamadee, Nur H., Joseph, Sabrina, Dolpady, Jayashree, Atarashi, Koji, Honda, Kenya, Zolezzi, Francesca, Poidinger, Michael, Lafaille, Juan J., de Lafaille, Maria A. Curotto

SCIENTIFIC REPORTS 6 2016.10

Research paper (scientific journal),  ISSN  2045-2322

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The microbiota in adaptive immune homeostasis and disease

Honda, Kenya, Littman, Dan R.

NATURE 535 ( 7610 ) 75 - 84 2016.07

Research paper (scientific journal),  ISSN  0028-0836

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Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers

Saito, Takuro, Nishikawa, Hiroyoshi, Wada, Hisashi, Nagano, Yuji, Sugiyama, Daisuke, Atarashi, Koji, Maeda, Yuka, Hamaguchi, Masahide, Ohkura, Naganari, Sato, Eiichi, Nagase, Hirotsugu, Nishimura, Junichi, Yamamoto, Hirofumi, Takiguchi, Shuji, Tanoue, Takeshi, Suda, Wataru, Morita, Hidetoshi, Hattori, Masahira, Honda, Kenya, Mori, Masaki, Doki, Yuichiro, Sakaguchi, Shimon

NATURE MEDICINE 22 ( 6 ) 679 - + 2016.06

Research paper (scientific journal),  ISSN  1078-8956

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Diet-dependent, microbiota-independent regulation of IL-10-producing lamina propria macrophages in the small intestine

Ochi, Takanori, Feng, Yongjia, Kitamoto, Sho, Nagao-Kitamoto, Hiroko, Kuffa, Peter, Atarashi, Koji, Honda, Kenya, Teitelbaum, Daniel H., Kamada, Nobuhiko

SCIENTIFIC REPORTS 6   75 - 84 2016.06

Research paper (scientific journal),  ISSN  2045-2322

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Germinal responses in murine Peyer's Patches are regulated by a subpopulation of microbiota-induced IL-21(high) Tfh cells

Jones, Leigh A., Ho, Wen Qi, Ying, Sze, Ramakrishna, Lakshmi, Srinivasan, Kandhadayar G., Yurieva, Marina, Ng, Wan Pei, Subramaniam, Sharrada, Hamadee, Nur H., Joseph, Sabrina, Dolpady, Jayashree, Atarashi, Koji, Honda, Kenya, Zolezzi, Francesca, Poidinger, Michael, Lafaille, Juan J., de Lafaille, Maria A. Curotto

JOURNAL OF IMMUNOLOGY 196 2016.05

Research paper (scientific journal),  ISSN  0022-1767

Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease

Mathewson, Nathan D., Jenq, Robert, Mathew, Anna V., Koenigsknecht, Mark, Hanash, Alan, Toubai, Tomomi, Oravecz-Wilson, Katherine, Wu, Shin-Rong, Sun, Yaping, Rossi, Corinne, Fujiwara, Hideaki, Byun, Jaeman, Shono, Yusuke, Lindemans, Caroline, Calafiore, Marco, Schmidt, Thomas C., Honda, Kenya, Young, Vincent B., Pennathur, Subramaniam, van den Brink, Marcel, Reddy, Pavan

NATURE IMMUNOLOGY 17 ( 5 ) 505 - + 2016.05

Research paper (scientific journal),  ISSN  1529-2908

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Helminth infection promotes colonization resistance via type 2 immunity

Ramanan, Deepshika, Bowcutt, Rowann, Lee, Soo Ching, Tang, Mei San, Kurtz, Zachary D., Ding, Yi,Honda, Kenya, Gause, William C., Blaser, Martin J., Bonneau, Richard A., Lim, Yvonne A. L., Loke, P'ng, Cadwell, Ken

SCIENCE 352 ( 6285 ) 608 - 612 2016.04

Research paper (scientific journal),  ISSN  0036-8075

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Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells

Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y, Narushima S, Suda W, Imaoka A, Setoyama H, Nagamori T, Ishikawa E, Shima T, Hara T, Kado S, Jinnohara T, Ohno H, Kondo T, Toyooka K, Watanabe E, Yokoyama S, Tokoro S, Mori H, Noguchi Y, Morita H, Ivanov II, Sugiyama T, Nuñez G, Camp JG, Hattori M, Umesaki* Y, Honda K*( *corresponding authors)

CELL 163 ( 2 ) 367 - 380 2015.10

Research paper (scientific journal), Joint Work

Microbiota-Dependent Activation of an Autoreactive T Cell Receptor Provokes Autoimmunity in an Immunologically Privileged Site.

Horai R, Zárate-Bladés CR, Dillenburg-Pilla P, Chen J, Kielczewski JL, Silver PB, Jittayasothorn Y, Chan CC, Yamane H, Honda K, Caspi RR.

IMMUNITY 43 ( 2 ) 343 - 353 2015.08

Research paper (scientific journal)

The microbiota regulates type 2 immunity through RORγt+ T cells

Ohnmacht C, Park JH, Cording S, Wing JB, Atarashi K, Obata Y, Gaboriau-Routhiau V, Marques R, Dulauroy S, Fedoseeva M, Busslinger M, Cerf-Bensussan N, Boneca IG, Voehringer D, Hase K, Honda K, Sakaguchi S, Eberl G

SCIENCE 349 ( 6251 ) 989 - 993 2015.08

Research paper (scientific journal), Joint Work, Accepted

Induction of Th17 cells by segmented filamentous bacteria in the murine intestine.

Farkas AM, Panea C, Goto Y, Nakato G, Galan-Diez M, Narushima S, Honda K, Ivanov ll

J Immunol Methods 421   104 - 111 2015.06

Research paper (scientific journal), Joint Work, Accepted

T-FH-IgA Responses Keep Microbiota in Check

Honda, Kenya

CELL HOST & MICROBE 17 ( 2 ) 144 - 146 2015.02

Research paper (scientific journal),  ISSN  1931-3128

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Foxp3(+) T Cells Regulate Immunoglobulin A Selection and Facilitate Diversification of Bacterial Species Responsible for Immune Homeostasis

Kawamoto, Shimpei, Maruya, Mikako, Kato, Lucia M., Suda, Wataru, Atarashi, Koji, Doi, Yasuko, Tsutsui, Yumi, Qin, Hongyan, Honda, Kenya, Okada, Takaharu, Hattori, Masahira, Fagarasan, Sidonia

IMMUNITY 41 ( 1 ) 152 - 165 2014.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1074-7613

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The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells

Obata, Yuuki, Furusawa, Yukihiro, Endo, Takaho A., Sharif, Jafar, Takahashi, Daisuke, Atarashi, Koji, Nakayama, Manabu, Onawa, Satoshi, Fujimura, Yumiko, Takahashi, Masumi, Ikawa, Tomokatsu, Otsubo, Takeshi, Kawamura, Yuki I., Dohi, Taeko, Tajima, Shoji, Masumoto, Hiroshi, Ohara, Osamu, Honda, Kenya, Hori, Shohei, Ohno, Hiroshi, Koseki, Haruhiko, Hase, Koji

NATURE IMMUNOLOGY 15 ( 6 ) 571 - 579 2014.06

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1529-2908

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Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells

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

NATURE 504 ( 7480 ) 446 - + 2013.12

Research paper (scientific journal),  ISSN  0028-0836

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Monocyte-Derived Dendritic Cells Perform Hemophagocytosis to Fine-Tune Excessive Immune Responses

Ohyagi, Hideaki, Onai, Nobuyuki, Sato, Taku, Yotsumoto, Satoshi, Liu, Jiajia, Akiba, Hisaya, Yagita, Hideo, Atarashi, Koji, Honda, Kenya, Roers, Axel, Mueller, Werner, Kurabayashi, Kazutaka, Hosoi-Amaike, Mayuka, Takahashi, Naoto, Hirokawa, Makoto, Matsushima, Kouji, Sawada, Kenichi, Ohteki, Toshiaki

IMMUNITY 39 ( 3 ) 584 - 598 2013.09

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1074-7613

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T-reg induction by a rationally selected mixture of Clostridia strains from the human microbiota

Atarashi, Koji, Tanoue, Takeshi, Oshima, Kenshiro, Suda, Wataru, Nagano, Yuji, Nishikawa, Hiroyoshi, Fukuda, Shinji, Saito, Takuro, Narushima, Seiko, Hase, Koji, Kim, Sangwan, Fritz, Joelle V., Wilmes, Paul, Ueha, Satoshi, Matsushima, Kouji, Ohno, Hiroshi, Olle, Bernat, Sakaguchi, Shimon, Taniguchi, Tadatsugu, Morita, Hidetoshi, Hattori, Masahira, Honda, Kenya

NATURE 500 ( 7461 ) 232 - + 2013.08

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0028-0836

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Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome

Yoshimoto, Shin, Loo, Tze Mun, Atarashi, Koji, Kanda, Hiroaki, Sato, Seidai, Oyadomari, Seiichi, Iwakura, Yoichiro, Oshima, Kenshiro, Morita, Hidetoshi, Hattori, Masahisa, Honda, Kenya, Ishikawa, Yuichi, Hara, Eiji, Ohtani, Naoko

NATURE 499 ( 7456 ) 97 - + 2013.07

Research paper (scientific journal),  ISSN  0028-0836

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Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome

Yoshimoto, Shin, Loo, Tze Mun, Atarashi, Koji, Kanda, Hiroaki, Sato, Seidai, Oyadomari, Seiichi, Iwakura, Yoichiro, Oshima, Kenshiro, Morita, Hidetoshi, Hattori, Masahisa, Honda, Kenya, Ishikawa, Yuichi, Hara, Eiji, Ohtani, Naoko

NATURE 499 ( 7456 ) 97 - 101 2013.07

Research paper (scientific journal), Accepted,  ISSN  0028-0836

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IRF4 Transcription Factor- Dependent CD11b(+) Dendritic Cells in Human and Mouse Control Mucosal IL-17 Cytokine Responses

Schlitzer, Andreas, McGovern, Naomi, Teo, Pearline, Zelante, Teresa, Atarashi, Koji, Low, Donovan, Ho, Adrian W. S., See, Peter, Shin, Amanda, Wasan, Pavandip Singh, Hoeffel, Guillaume, Malleret, Benoit, Heiseke, Alexander, Chew, Samantha, Jardine, Laura, Purvis, Harriet A., Hilkens, Catharien M. U., Tam, John, Poidinger, Michael, Stanley, E. Richard, Krug, Anne B., Renia, Laurent, Sivasankar, Baalasubramanian, Lai Guan Ng, Collin, Matthew, Ricciardi-Castagnoli, Paola, Honda, Kenya, Haniffa, Muzlifah, Ginhoux, Florent

IMMUNITY 38 ( 5 ) 970 - 983 2013.05

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1074-7613

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Transcriptional reprogramming of mature CD4(+) helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes

Mucida, Daniel, Husain, Mohammad Mushtaq, Muroi, Sawako, van Wijk, Femke, Shinnakasu, Ryo, Naoe, Yoshinori, Reis, Bernardo Sgarbi, Huang, Yujun, Lambolez, Florence, Docherty, Michael, Attinger, Antoine, Shui, Jr-Wen, Kim, Gisen, Lena, Christopher J., Sakaguchi, Shinya, Miyamoto, Chizuko, Wang, Peng, Atarashi, Koji, Park, Yunji, Nakayama, Toshinori, Honda, Kenya, Ellmeier, Wilfried, Kronenberg, Mitchell, Taniuchi, Ichiro, Cheroutre, Hilde

NATURE IMMUNOLOGY 14 ( 3 ) 281 - 289 2013.03

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1529-2908

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Essential contribution of IRF3 to intestinal homeostasis and microbiota-mediated Tslp gene induction

Negishi, Hideo, Miki, Shoji, Sarashina, Hana, Taguchi-Atarashi, Naoko, Nakajima, Akira, Matsuki, Kosuke, Endo, Nobuyasu, Yanai, Hideyuki, Nishio, Junko, Honda, Kenya, Taniguchi, Tadatsugu

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109 ( 51 ) 21016 - 21021 2012.12

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0027-8424

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Intestinal Commensal Microbes as Immune Modulators

Ivanov, Ivaylo I., Honda, Kenya

CELL HOST & MICROBE 12 ( 4 ) 496 - 508 2012.10

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1931-3128

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Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses

Negishi, Hideo, Yanai, Hideyuki, Nakajima, Akira, Koshiba, Ryuji, Atarashi, Koji, Matsuda, Atsushi, Matsuki, Kosuke, Miki, Shoji, Doi, Takahiro, Aderem, Alan, Nishio, Junko, Smale, Stephen T., Honda, Kenya, Taniguchi, Tadatsugu

NATURE IMMUNOLOGY 13 ( 7 ) 659 - 666 2012.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1529-2908

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The Microbiome in Infectious Disease and Inflammation

Honda, Kenya, Littman, Dan R.

ANNUAL REVIEW OF IMMUNOLOGY, VOL 30 30   759 - 795 2012

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0732-0582

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Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species

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

SCIENCE 331 ( 6015 ) 337 - 341 2011.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0036-8075

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Contribution of IRF5 in B cells to the development of murine SLE-like disease through its transcriptional control of the IgG2a locus

Savitsky, David A., Yanai, Hideyuki, Tamura, Tomohiko, Taniguchi, Tadatsugu, Honda, Kenya

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 107 ( 22 ) 10154 - 10159 2010.06

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0027-8424

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HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses

Yanai, Hideyuki, Ban, Tatsuma, Wang, ZhiChao, Choi, Myoung Kwon, Kawamura, Takeshi, Negishi, Hideo, Nakasato, Makoto, Lu, Yan, Hangai, Sho, Koshiba, Ryuji, Savitsky, David, Ronfani, Lorenza, Akira, Shizuo, Bianchi, Marco E., Honda, Kenya, Tamura, Tomohiko, Kodama, Tatsuhiko, Taniguchi, Tadatsugu

NATURE 462 ( 7269 ) 99 - 103 2009.11

Research paper (scientific journal), Accepted,  ISSN  0028-0836

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Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria

Ivanov, Ivaylo I., Atarashi, Koji, Manel, Nicolas, Brodie, Eoin L., Shima, Tatsuichiro, Karaoz, Ulas, Wei, Dongguang, Goldfarb, Katherine C., Santee, Clark A., Lynch, Susan V., Tanoue, Takeshi, Imaoka, Akemi, Itoh, Kikuji, Takeda, Kiyoshi, Umesaki, Yoshinori, Honda, Kenya, Littman, Dan R.

CELL 139 ( 3 ) 485 - 498 2009.10

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0092-8674

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A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity

Negishi, Hideo, Osawa, Tomoko, Ogami, Kentaro, Ouyang, Xinshou, Sakaguchi, Shinya, Koshiba, Ryuji, Yanai, Hideyuki, Seko, Yoshinori, Shitara, Hiroshi, Bishop, Keith, Yonekawa, Hiromichi, Tamura, Tomohiko, Kaisho, Tsuneyasu, Taya, Choji, Taniguchi, Tadatsugu, Honda, Kenya

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 105 ( 51 ) 20446 - 20451 2008.12

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0027-8424

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ATP drives lamina propria T(H)17 cell differentiation

Atarashi, Koji, Nishimura, Junichi, Shima, Tatsuichiro, Umesaki, Yoshinori, Yamamoto, Masahiro, Onoue, Masaharu, Yagita, Hideo, Ishii, Naoto, Evans, Richard, Honda, Kenya, Takeda, Kiyoshi

NATURE 455 ( 7214 ) 808 - 812 2008.10

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0028-0836

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The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and T(H)1 versus T-H-17 differentiation of CD4(+) T cells

Kano, Shin-ichi, Sato, Kojiro, Morishita, Yasyuki, Vollstedt, Sabine, Kim, Sunhwa, Bishop, Keith, Honda, Kenya, Kubo, Masato, Taniguchi, Tadatsugu

NATURE IMMUNOLOGY 9 ( 1 ) 34 - 41 2008.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1529-2908

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DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response

Takaoka, Akinori, Wang, ZhiChao, Choi, Myoung Kwon, Yanai, Hideyuki, Negishi, Hideo, Ban, Tatsuma, Lu, Yan, Miyagishi, Makoto, Kodama, Tatsuhiko, Honda, Kenya, Ohba, Yusuke, Taniguchi, Tadatsugu

NATURE 448 ( 7152 ) 501 - 505 2007.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0028-0836

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Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression

Yanai, Hideyuki, Chen, Hui-min, Inuzuka, Takayuki, Kondo, Seiji, Mak, Tak W., Takaoka, Akinori, Honda, Kenya, Taniguchi, Tadatsugu

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 104 ( 9 ) 3402 - 3407 2007.02

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0027-8424

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Type I interferon gene induction by the interferon regulatory factor family of transcription factors (vol 25, pg 349, 2006)

Honda, Kenya, Takaoka, Akinori, Taniguchi, Tadatsugu

IMMUNITY 25   349 - 360 2006.11

Research paper (scientific journal), Joint Work,  ISSN  1074-7613

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Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program

Negishi, Hideo, Fujita, Yasuyuki, Yanai, Hideyuki, Sakaguchi, Shinya, Ouyang, Xinshou, Shinohara, Masahiro, Takayanagi, Hiroshi, Ohba, Yusuke, Taniguchi, Tadatsugu, Honda, Kenya

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 103 ( 41 ) 15136 - 15141 2006.10

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0027-8424

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IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors

Honda, Kenya, Taniguchi, Tadatsugu

NATURE REVIEWS IMMUNOLOGY 6   644 - 658 2006.09

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1474-1733

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Negative regulation of Toll-like-receptor signaling by IRF-4.

Hideo Negishi, Yusuke Ohba, Hideyuki Yanai, Akinori Takaoka, Kiri Honma, Katsuyuki Yui, Toshifumi Matsuyama, Tadatsugu Taniguchi, and Kenya Honda

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 102 ( 44 ) 15989 - 15994 2005.11

Joint Work, Accepted

Spatiotemporal regulation of MyD88–IRF-7 signalling for robust type-I interferon induction

Kenya Honda, Yusuke Ohba, Hideyuki Yanai, Hideo Negishi, Tatsuaki Mizutani, Akinori Takaoka, Choji Taya, Tadatsugu Taniguchi

NATURE 434   1035 - 1040 2005.04

Joint Work

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IRF-7 is the master regulator of type-I interferon-dependent immune responses

Kenya Honda, Hideyuki Yanai, Hideo Negishi, Masataka Asagiri, Mitsuharu Sato, Tatsuaki Mizutani, Naoya Shimada, Yusuke Ohba, Akinori Takaoka, Nobuaki Yoshida, Tadatsugu Taniguchi

NATURE 434   772 - 777 2005.03

Joint Work, Accepted

Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling

Kenya Honda, Hideyuki Yanai, Tatsuaki Mizutani, Hideo Negishi, Naoya Shimada, Nobutaka Suzuki, Yusuke Ohba, Akinori Takaoka, Wen-Chen Yeh, Tadatsugu Taniguchi

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 101 ( 43 ) 15416 - 15421 2004.10

Joint Work, Accepted

Negative regulation of IFN-alpha/beta signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells.

Kenya Honda, Tatsuaki Mizutani, Tadatsugu Taniguchi

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 101 ( 8 ) 2416 - 2421 2004.02

Research paper (scientific journal), Joint Work, Accepted

Selective contribution of IFN-α/β signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection

Kenya Honda, Shinya Sakaguchi, Chigusa Nakajima, Ai Watanabe, Hideyuki Yanai, Misako Matsumoto, Toshiaki Ohteki, Tsuneyasu Kaisho, Akinori Takaoka, Shizuo Akira, Tsukasa Seya, Tadatsugu Taniguchi

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 100 ( 19 ) 10872 - 10877 2003.09

Research paper (scientific journal), Joint Work, Accepted

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Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence

Akinori Takaoka, Sumio Hayakawa, Hideyuki Yanai, Dagmar Stoiber, Hideo Negishi, Hideaki Kikuchi, Shigeru Sasaki, Kohzoh Imai, Tsukasa Shibue, Kenya Honda, Tadatsugu Taniguchi

NATURE 424   516 - 523 2003.07

Research paper (scientific journal), Joint Work, Accepted

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Molecular Basis for Hematopoietic/Mesenchymal Interaction during Initiation of Peyer's Patch Organogenesis

Kenya Honda,Hiroyasu Nakano, Hisahiro Yoshida, Satomi Nishikawa, Paul Rennert, Koichi Ikuta, Masakatsu Tamechika, Kazuhito Yamaguchi, Tetsuo Fukumoto, Tsutomu Chiba, Shin-Ichi Nishikawa

The Journal of Experimental Medicine (JEM) 193 ( 5 ) 621 - 630 2001.03

Research paper (scientific journal), Joint Work, Accepted