Hiroshi Kiyono

High frequency oscillatory ventilation attenuates the activation of alveolar macrophages and neutrophils in lung injury (1998)

Shimaoku, Motomu, Fujino, Yuji, Taenaka, Nobuyuki, Hiroi, Takachika, Kiyono, Hiroshi, Yoshiya, Ikuto

Abstract Background Recent investigations have shown that leukocyte activation is involved in the pathogenesis of ventilator-associated lung injury. This study was designed to investigate whether the...

Characteristics of claudin expression in follicle-associated epithelium of Peyer's patches: Preferential localization of claudin-4 at the apex of the dome region

Tamagawa, Hiroshi, Takahashi, Ichiro, 高橋, 一郎, タカハシ, イチロウ, Takahashi, Ichirō, Furuse, Mikio, ...

Gut-associated lymphoreticular tissue (GALT), such as Peyer's patches (PP) and cecal patches, are important inductive sites for mucosal immune responses. As such, the GALT may have an epithelial...

A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity

Yamamoto, Shingo, Kiyono, Hiroshi, Yamamoto, Masafumi, Imaoka, Koichi, Yamamoto, Miho, Fujihashi, Kohtaro, ...

We have characterized a nontoxic mutant of cholera toxin (CT) as a mucosal adjuvant in mice. The mutant CT was made by substitution of serine with phenylalanine at position 61 of the A subunit...

Peyer's patches are required for oral tolerance to proteins

Fujihashi, Kohtaro, Dohi, Taeko, Rennert, Paul D., Yamamoto, Masafumi, Koga, Toshiya, Kiyono, Hiroshi, ...

To clarify the role of Peyer's patches in oral tolerance induction, BALB/c mice were treated in utero with lymphotoxin β-receptor Ig fusion protein to generate mice lacking Peyer's patches. When...

Expression of Recombinant Enterotoxigenic Escherichia coli Colonization Factor Antigen I by Salmonella typhimurium Elicits a Biphasic T Helper Cell Response

Pascual, David W., Hone, David M., Hall, Stacy, Van Ginkel, Frederik W., Yamamoto, Masafumi, Walters, Nancy, ...

Protective immunity to enterotoxigenic Escherichia coli (ETEC) is antibody (Ab) dependent; however, oral immunization with purified ETEC fimbriae fails to elicit protective immunity as a consequence...

Mucosally Induced Immunoglobulin E-Associated Inflammation in the Respiratory Tract

Simecka, Jerry W., Jackson, Raymond J., Kiyono, Hiroshi, McGhee, Jerry R.

The purpose of the present study was to determine the immunologic responses, particularly immunopathologic reactions, associated with nasal immunization with the mucosal adjuvant, cholera toxin (CT)....

Immunoglobulin A (IgA) Responses and IgE-Associated Inflammation along the Respiratory Tract after Mucosal but Not Systemic Immunization

Hodge, Lisa M., Marinaro, Mariarosaria, Jones, Harlan P., McGhee, Jerry R., Kiyono, Hiroshi, Simecka, Jerry W.

The purpose of the present study was to determine the extent of immunologic responses, particularly immunopathologic responses, within the upper and lower respiratory tracts after intranasal...

Influenza Virus-Infected Epithelial Cells Present Viral Antigens to Antigen-Specific CD8+ Cytotoxic T Lymphocytes

Nguyen, Huan H., Boyaka, Prosper N., Moldoveanu, Zina, Novak, Miroslav J., Kiyono, Hiroshi, McGhee, Jerry R., ...

We have investigated the mechanisms involved in the clearance of viral infection at the epithelium level by analyzing the activity of influenza virus-specific cytotoxic T lymphocytes (CTL) against...

Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice

Kobayashi, Masaya, Kweon, Mi-Na, Kuwata, Hirotaka, Schreiber, Robert D., Kiyono, Hiroshi, Takeda, Kiyoshi, ...

Stat3 plays an essential role in IL-10 signaling pathways. A myeloid cell-specific deletion of Stat3 resulted in inflammatory cytokine production and development of chronic enterocolitis with...

Systemically derived large intestinal CD4+ Th2 cells play a central role in STAT6-mediated allergic diarrhea

Kweon, Mi-Na, Yamamoto, Masafumi, Kajiki, Masahiro, Takahashi, Ichiro, Kiyono, Hiroshi

Systemically primed BALB/c mice developed severe diarrhea after repeated oral administration of ovalbumin (OVA). Histological analysis demonstrated that dramatic infiltration of eosinophils and mast...

In vitro immune responses to a T cell-dependent antigen by cultures of disassociated murine Peyer's patch

Kiyono, Hiroshi, McGhee, Jerry R., Wannemuehler, Michael J., Frangakis, Maria V., Spalding, David M., Michalek, Suzanne M., ...

The first line of defense against pathogens that enter the host by the oral route appears to involve the gut-associated lymphoreticular tissue—e.g., Peyer's patches (PP). Although animals can...

Intestinal villous M cells: An antigen entry site in the mucosal epithelium

Jang, Myoung Ho, Kweon, Mi-Na, Iwatani, Koichi, Yamamoto, Masafumi, Terahara, Kazutaka, Sasakawa, Chihiro, ...

M cells located in the follicle-associated epithelium of Peyer's patches (PP) are shown to be the principal sites for the sampling of gut luminal antigens. Thus, PP have long been considered the...

Virulence of Streptococcus mutans: Restoration of Pathogenesis of a Glucosyltransferase-Defective Mutant (C4)

Hirasawa, Masatomo, Kiyono, Hiroshi, Shiota, Tetsuo, Hull, Richard A., Curtiss, Roy, Michalek, Suzanne M., ...

Previous studies have shown that a mutant (designated C4) of Streptococcus mutans 6715 wild type (WT) is defective in glucosyltransferase (GTF)-synthesized insoluble glucan and is avirulent in...

Virulence of Streptococcus mutans: In Vivo Reversion of a Low-Virulence Mutant Results in Partial Displacement and Pathogenesis

Hirasawa, Masatoma, Kiyono, Hiroshi, Babb, James L., Shiota, Tetsuo, Michalek, Suzanne M., McGhee, Jerry R.

A mutant of Streptococcus mutans 6715 wild type (WT), designated C4, has been shown previously to be defective in glucosyltransferase synthesis of insoluble glucan and to have low virulence in...

Nontoxic Shiga Toxin Derivatives from Escherichia coli Possess Adjuvant Activity for the Augmentation of Antigen-Specific Immune Responses via Dendritic Cell Activation

Ohmura, Mari, Yamamoto, Masafumi, Tomiyama-Miyaji, Chikako, Yuki, Yoshikazu, Takeda, Yoshifumi, Kiyono, Hiroshi

Shiga toxin (Stx) derivatives, such as the Stx1 B subunit (StxB1), which mediates toxin binding to the membrane, and mutant Stx1 (mStx1), which is a nontoxic doubly mutated Stx1 harboring amino acid...

A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses

Takagi, Hidenori, Hiroi, Takachika, Yang, Lijun, Tada, Yoshifumi, Yuki, Yoshikazu, Takamura, Kaoru, ...

Peptide immunotherapy using multiple predominant allergen-specific T cell epitopes is a safe and promising strategy for the control of type I allergy. In this study, we developed transgenic rice...

A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity

Yamamoto, Shingo, Kiyono, Hiroshi, Yamamoto, Masafumi, Imaoka, Koichi, Yamamoto, Miho, Fujihashi, Kohtaro, ...

We have characterized a nontoxic mutant of cholera toxin (CT) as a mucosal adjuvant in mice. The mutant CT was made by substitution of serine with phenylalanine at position 61 of the A subunit...

Peyer's patches are required for oral tolerance to proteins

Fujihashi, Kohtaro, Dohi, Taeko, Rennert, Paul D., Yamamoto, Masafumi, Koga, Toshiya, Kiyono, Hiroshi, ...

To clarify the role of Peyer's patches in oral tolerance induction, BALB/c mice were treated in utero with lymphotoxin β-receptor Ig fusion protein to generate mice lacking Peyer's patches. When...

Expression of Recombinant Enterotoxigenic Escherichia coli Colonization Factor Antigen I by Salmonella typhimurium Elicits a Biphasic T Helper Cell Response

Pascual, David W., Hone, David M., Hall, Stacy, Van Ginkel, Frederik W., Yamamoto, Masafumi, Walters, Nancy, ...

Protective immunity to enterotoxigenic Escherichia coli (ETEC) is antibody (Ab) dependent; however, oral immunization with purified ETEC fimbriae fails to elicit protective immunity as a consequence...

Mucosally Induced Immunoglobulin E-Associated Inflammation in the Respiratory Tract

Simecka, Jerry W., Jackson, Raymond J., Kiyono, Hiroshi, McGhee, Jerry R.

The purpose of the present study was to determine the immunologic responses, particularly immunopathologic reactions, associated with nasal immunization with the mucosal adjuvant, cholera toxin (CT)....

Immunoglobulin A (IgA) Responses and IgE-Associated Inflammation along the Respiratory Tract after Mucosal but Not Systemic Immunization

Hodge, Lisa M., Marinaro, Mariarosaria, Jones, Harlan P., McGhee, Jerry R., Kiyono, Hiroshi, Simecka, Jerry W.

The purpose of the present study was to determine the extent of immunologic responses, particularly immunopathologic responses, within the upper and lower respiratory tracts after intranasal...

Influenza Virus-Infected Epithelial Cells Present Viral Antigens to Antigen-Specific CD8+ Cytotoxic T Lymphocytes

Nguyen, Huan H., Boyaka, Prosper N., Moldoveanu, Zina, Novak, Miroslav J., Kiyono, Hiroshi, McGhee, Jerry R., ...

We have investigated the mechanisms involved in the clearance of viral infection at the epithelium level by analyzing the activity of influenza virus-specific cytotoxic T lymphocytes (CTL) against...

Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice

Kobayashi, Masaya, Kweon, Mi-Na, Kuwata, Hirotaka, Schreiber, Robert D., Kiyono, Hiroshi, Takeda, Kiyoshi, ...

Stat3 plays an essential role in IL-10 signaling pathways. A myeloid cell-specific deletion of Stat3 resulted in inflammatory cytokine production and development of chronic enterocolitis with...

Systemically derived large intestinal CD4+ Th2 cells play a central role in STAT6-mediated allergic diarrhea

Kweon, Mi-Na, Yamamoto, Masafumi, Kajiki, Masahiro, Takahashi, Ichiro, Kiyono, Hiroshi

Systemically primed BALB/c mice developed severe diarrhea after repeated oral administration of ovalbumin (OVA). Histological analysis demonstrated that dramatic infiltration of eosinophils and mast...

In vitro immune responses to a T cell-dependent antigen by cultures of disassociated murine Peyer's patch

Kiyono, Hiroshi, McGhee, Jerry R., Wannemuehler, Michael J., Frangakis, Maria V., Spalding, David M., Michalek, Suzanne M., ...

The first line of defense against pathogens that enter the host by the oral route appears to involve the gut-associated lymphoreticular tissue—e.g., Peyer's patches (PP). Although animals can...

Intestinal villous M cells: An antigen entry site in the mucosal epithelium

Jang, Myoung Ho, Kweon, Mi-Na, Iwatani, Koichi, Yamamoto, Masafumi, Terahara, Kazutaka, Sasakawa, Chihiro, ...

M cells located in the follicle-associated epithelium of Peyer's patches (PP) are shown to be the principal sites for the sampling of gut luminal antigens. Thus, PP have long been considered the...

Virulence of Streptococcus mutans: Restoration of Pathogenesis of a Glucosyltransferase-Defective Mutant (C4)

Hirasawa, Masatomo, Kiyono, Hiroshi, Shiota, Tetsuo, Hull, Richard A., Curtiss, Roy, Michalek, Suzanne M., ...

Previous studies have shown that a mutant (designated C4) of Streptococcus mutans 6715 wild type (WT) is defective in glucosyltransferase (GTF)-synthesized insoluble glucan and is avirulent in...

Virulence of Streptococcus mutans: In Vivo Reversion of a Low-Virulence Mutant Results in Partial Displacement and Pathogenesis

Hirasawa, Masatoma, Kiyono, Hiroshi, Babb, James L., Shiota, Tetsuo, Michalek, Suzanne M., McGhee, Jerry R.

A mutant of Streptococcus mutans 6715 wild type (WT), designated C4, has been shown previously to be defective in glucosyltransferase synthesis of insoluble glucan and to have low virulence in...

Nontoxic Shiga Toxin Derivatives from Escherichia coli Possess Adjuvant Activity for the Augmentation of Antigen-Specific Immune Responses via Dendritic Cell Activation

Ohmura, Mari, Yamamoto, Masafumi, Tomiyama-Miyaji, Chikako, Yuki, Yoshikazu, Takeda, Yoshifumi, Kiyono, Hiroshi

Shiga toxin (Stx) derivatives, such as the Stx1 B subunit (StxB1), which mediates toxin binding to the membrane, and mutant Stx1 (mStx1), which is a nontoxic doubly mutated Stx1 harboring amino acid...

A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses

Takagi, Hidenori, Hiroi, Takachika, Yang, Lijun, Tada, Yoshifumi, Yuki, Yoshikazu, Takamura, Kaoru, ...

Peptide immunotherapy using multiple predominant allergen-specific T cell epitopes is a safe and promising strategy for the control of type I allergy. In this study, we developed transgenic rice...

Characteristics of claudin expression in follicle-associated epithelium of Peyer's patches: Preferential localization of claudin-4 at the apex of the dome region

Tamagawa, Hiroshi, Takahashi, Ichiro, 高橋, 一郎, タカハシ, イチロウ, Takahashi, Ichirō, Furuse, Mikio, ...

Gut-associated lymphoreticular tissue (GALT), such as Peyer's patches (PP) and cecal patches, are important inductive sites for mucosal immune responses. As such, the GALT may have an epithelial...

Pathological Role of Large Intestinal IL-12p40 for the Induction of Th2-Type Allergic Diarrhea

Hino, Ayako, Kweon, Mi-Na, Fujihashi, Kohtaro, McGhee, Jerry R., Kiyono, Hiroshi

IL-12 consists of two disulfide-linked subunits, p40 and p35, that form functionally active heterodimers for the induction of Th1 cells. In contrast to IL-12 heterodimers, p40 monomers and homodimers...

Human Nasopharyngeal-Associated Lymphoreticular Tissues : Functional Analysis of Subepithelial and Intraepithelial B and T Cells from Adenoids and Tonsils

Boyaka, Prosper N., Wright, Peter F., Marinaro, Mariarosaria, Kiyono, Hiroshi, Johnson, Joyce E., Gonzales, Ricardo A., ...

Subepithelial and intraepithelial lymphocytes of human adenoids and tonsils were characterized and directly compared to determine the potential contribution of these tissues to mucosal and systemic...

Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis

Nagai, Shigenori, Mimuro, Hitomi, Yamada, Taketo, Baba, Yukiko, Moro, Kazuyo, Nochi, Tomonori, ...

Helicobacter pylori is a Gram-negative spiral bacterium that causes gastritis and peptic ulcer and has been implicated in the pathogenesis of gastric adenocarcinoma and mucosa-associated lymphoid...

Establishment of a Poliovirus Oral Infection System in Human Poliovirus Receptor-Expressing Transgenic Mice That Are Deficient in Alpha/Beta Interferon Receptor▿

Ohka, Seii, Igarashi, Hiroko, Nagata, Noriyo, Sakai, Mai, Koike, Satoshi, Nochi, Tomonori, ...

Poliovirus (PV) is easily transferred to humans orally; however, no rodent model for oral infections has been developed because of the alimentary tract's low sensitivity to the virus. Here we showed...

Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination

Nochi, Tomonori, Takagi, Hidenori, Yuki, Yoshikazu, Yang, Lijun, Masumura, Takehiro, Mejima, Mio, ...

Capable of inducing antigen-specific immune responses in both systemic and mucosal compartments without the use of syringe and needle, mucosal vaccination is considered ideal for the global control...

Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium

Kunisawa, Jun, Kurashima, Yosuke, Higuchi, Morio, Gohda, Masashi, Ishikawa, Izumi, Ogahara, Ikuko, ...

It is well established that intraepithelial T lymphocytes (IELs) are derived from conventional single-positive (SP) thymocytes, as well as unconventional double-negative (DN) thymocytes and...

Hapten-induced Colitis Is Associated with Colonic Patch Hypertrophy and T Helper Cell 2–Type Responses

Dohi, Taeko, Fujihashi, Kohtaro, Rennert, Paul D., Iwatani, Koichi, Kiyono, Hiroshi, McGhee, Jerry R.

To investigate the potential involvement of T helper (Th)2-type responses in murine models of intestinal inflammation, we used trinitrobenzene sulfonic acid (TNBS)–hapten to induce inflammatory...

Alteration of Interleukin 4 Production Results in the Inhibition of T Helper Type 2 Cell–Dominated Inflammatory Bowel Disease in T Cell Receptor α Chain–Deficient Mice

Iijima, Hideki, Takahashi, Ichiro, Kishi, Daisuke, Kim, Jin-Kyung, Kawano, Sunao, Hori, Masatsugu, ...

T cell receptor α chain–deficient (TCR-α−/−) mice are known to spontaneously develop inflammatory bowel disease (IBD). The colitis that develops in these mice is associated with increased...

Oral but Not Parenteral Interleukin (IL)-12 Redirects T Helper 2 (Th2)-type Responses to an Oral Vaccine Without Altering Mucosal IgA Responses

Marinaro, Mariarosaria, Boyaka, Prosper N., Finkelman, Fred D., Kiyono, Hiroshi, Jackson, Raymond J., Jirillo, Emilio, ...

Our past studies have shown that the mucosal adjuvant cholera toxin (CT) induces T helper type 2 (Th2) responses with systemic IgG1, IgE and mucosal secretory IgA (S-IgA) antibodies (Abs). In this...

Mutants in the ADP-ribosyltransferase Cleft of Cholera Toxin Lack Diarrheagenicity but Retain Adjuvanticity

Yamamoto, Shingo, Takeda, Yoshifumi, Yamamoto, Masafumi, Kurazono, Hisao, Imaoka, Koichi, Yamamoto, Miho, ...

Cholera toxin (CT), the most commonly used mucosal adjuvant in experimental animals, is unsuitable for humans because of potent diarrhea-inducing properties. We have constructed two CT-A subunit...

A novel M cell–specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses

Nochi, Tomonori, Yuki, Yoshikazu, Matsumura, Akiko, Mejima, Mio, Terahara, Kazutaka, Kim, Dong-Young, ...

Mucosally ingested and inhaled antigens are taken up by membranous or microfold cells (M cells) in the follicle-associated epithelium of Peyer's patches or nasopharynx-associated lymphoid tissue. We...

Peyer's Patches Are Required for Intestinal Immunoglobulin A Responses to Salmonella spp.▿

Hashizume, Tomomi, Togawa, Atsushi, Nochi, Tomonori, Igarashi, Osamu, Kweon, Mi-Na, Kiyono, Hiroshi, ...

Previous studies have shown that Peyer's patches (PP) are not required for intestinal immunoglobulin A (IgA) responses to orally administered soluble protein. However, the roles of PP in regulation...