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Article ; Online: Genetic Susceptibility of the Host in Virus-Induced Diabetes

Keiichiro Mine / Yasunobu Yoshikai / Hirokazu Takahashi / Hitoe Mori / Keizo Anzai / Seiho Nagafuchi

Microorganisms, Vol 8, Iss 1133, p

2020 Volume 1133

Abstract: Enteroviruses, especially Coxsackie B viruses, are among the candidate environmental factors causative of type 1 diabetes. Host genetic factors have an impact on the development of virus-induced diabetes (VID). Host background, in terms of whether the ... ...

Abstract	Enteroviruses, especially Coxsackie B viruses, are among the candidate environmental factors causative of type 1 diabetes. Host genetic factors have an impact on the development of virus-induced diabetes (VID). Host background, in terms of whether the host is prone to autoimmunity, should also be considered when analyzing the role of target genes in VID. In this review, we describe the genetic susceptibility of the host based on studies in humans and VID animal models. Understanding the host genetic factors should contribute not only to revealing the mechanisms of VID development, but also in taking measures to prevent VID.
Keywords	diabetes ; virus ; susceptibility genes ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CD5âNK1.1+ Î³Î´ T Cells that Develop in a Bcl11b-Independent Manner Participate in Early Protection against Infection

Shinya Hatano / Tesshin Murakami / Naoto Noguchi / Hisakata Yamada / Yasunobu Yoshikai

Cell Reports, Vol 21, Iss 5, Pp 1191-

2017 Volume 1202

Abstract: Summary: We recently found that a unique subset of innate-like Î³Î´ TÂ cells develops from the DN2a stage of the fetal thymus independently of the zinc-finger transcription factor B cell leukemia/lymphoma 11b (Bcl11b). Herein, we characterize these ... ...

Abstract	Summary: We recently found that a unique subset of innate-like Î³Î´ TÂ cells develops from the DN2a stage of the fetal thymus independently of the zinc-finger transcription factor B cell leukemia/lymphoma 11b (Bcl11b). Herein, we characterize these Bcl11b-independent Î³Î´ TÂ cells in the periphery as CD5âNK1.1+ and Granzyme B+, and we show that they are capable of producing interferon (IFN)-Î³ upon TÂ cell receptor stimulation without Ca2+ influx. In wild-type mice, these cells were sparse in lymphoid tissues but abundant in non-lymphoid tissues, such as the liver. Bcl11b-independent CD5âNK1.1+ Î³Î´ TÂ cells appeared and contributed to early protection before Bcl11b-dependent CD5+NK1.1â Î³Î´ TÂ cells following Listeria monocytogenes infection, resembling their sequential appearance during development in the thymus. : Bcl11b is essential for transition from the DN2a to the DN2b stage in the thymus. Hatano etÂ al. find that CD5âNK1.1+ Î³Î´ TÂ cells develop from the DN2a stage in a Bcl11b-independent manner and participate in host defense at an early stage after bacterial infection in periphery. Keywords: innate immunity, Î³Î´ TÂ cell, Bcl11b, DN2a, IFN-Î³, Granzyme, IL-17A, host defense, bacteria, Listeria monocytogenes
Keywords	Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2017-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effects of an 8-Week Protein Supplementation Regimen with Hyperimmunized Cow Milk on Exercise-Induced Organ Damage and Inflammation in Male Runners

Sihui Ma / Takaki Tominaga / Kazue Kanda / Kaoru Sugama / Chiaki Omae / Shunsuke Hashimoto / Katsuhiko Aoyama / Yasunobu Yoshikai / Katsuhiko Suzuki

Biomedicines, Vol 8, Iss 3, p

A Randomized, Placebo Controlled, Cross-Over Study

2020 Volume 51

Abstract: Prolonged strenuous exercise may induce inflammation, cause changes in gastrointestinal permeability, and lead to other unfavorable biological changes and diseases. Nutritional approaches have been used to prevent exercise-induced inflammatory responses ... ...

Abstract	Prolonged strenuous exercise may induce inflammation, cause changes in gastrointestinal permeability, and lead to other unfavorable biological changes and diseases. Nutritional approaches have been used to prevent exercise-induced inflammatory responses and gastrointestinal disorders. Hyperimmunized milk, obtained by immunizing cows against specific antigens, promotes the development of immunity against pathogens, promotes anti-inflammatory effects, and protects intestinal function. Immune protein (IMP) is a concentrated product of hyperimmunized milk and is a more promising means of supplementation to protect against acute infections and inflammation. To determine whether IMP has protective properties against exercise-induced gastrointestinal dysfunction and inflammation, we examined biochemical markers, intestinal damage markers, and pro-/anti-inflammatory profiles of young male runners using a randomized, placebo controlled, cross-over design. Urine samples were collected and used for measurements of creatinine, N -acetyl-β-d-glucosaminidase, osmotic pressure, and specific gravity. Titin was measured as a muscle damage marker. Further, urine concentrations of complement 5a, calprotectin, fractalkine, myeloperoxidase, macrophage colony-stimulating factor, monocyte chemotactic protein-1, intestinal fatty acid binding protein (I-FABP), interferon (IFN)-γ, interleukin (IL)-1β, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assays. We demonstrated that urine osmotic pressure, urine specific gravity, I-FABP, IFN-γ, IL-1β, and TNF-α were reduced by 8 weeks of IMP supplementation, indicating that IMP may have potential in preventing strenuous exercise-induced renal dysfunction, increased intestinal permeability, and inflammation. Thus, IMP supplementation may be a feasible nutritional approach for the prevention of unfavorable exercise-induced symptoms.
Keywords	hyperimmunized milk ; exercise ; inflammation ; intestinal permeability ; cytokine ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Oral intake of heat-killed Lactobacillus plantarum L-137 decreases the incidence of upper respiratory tract infection in healthy subjects with high levels of psychological stress

Yoshitaka Hirose / Yoshihiro Yamamoto / Yasunobu Yoshikai / Shinji Murosaki

Journal of Nutritional Science, Vol

2013 Volume 2

Abstract: The immunomodulatory effects of live or non-viable lactic acid bacteria have been extensively investigated. We reported that oral intake of heat-killed Lactobacillus plantarum L-137 (HK L-137) augmented innate and acquired immunity in mice and human ... ...

Abstract	The immunomodulatory effects of live or non-viable lactic acid bacteria have been extensively investigated. We reported that oral intake of heat-killed Lactobacillus plantarum L-137 (HK L-137) augmented innate and acquired immunity in mice and human subjects. To examine the effects of HK L-137 intake on upper respiratory tract infection (URTI) symptoms and immune functions in human subjects, a randomised, double-blind, placebo-controlled, parallel study was conducted in subjects with high psychological stress levels. A total of seventy-eight healthy subjects (thirty-three men and forty-five women; mean age 50·6 years) with scores of >41 on eighteen-item subscales of psychological distress in the Brief Job Stress Questionnaire were randomly assigned to receive a tablet containing HK L-137 (10 mg) or a placebo tablet daily for 12 weeks. The URTI symptoms were rated once daily on the validated twenty-one-item Wisconsin Upper Respiratory Symptom Survey-21. Immune functions, such as concanavalin A-induced proliferation and percentages of interferon (IFN)-γ- and IL-4-producing CD4 T cells of peripheral blood mononuclear cells (PBMC), and serum IFN-β concentrations were measured every 4 weeks. URTI incidence was significantly lower in the HK L-137 group than in the control group. URTI incidence, duration and severity, and duration of medication showed significant negative correlations with duration of HK L-137 intake. The percentage change from baseline of concanavalin A-induced proliferation of PBMC was significantly greater in the HK L-137 group than in the control group. These findings suggest that daily HK L-137 intake can decrease URTI incidence in healthy subjects, possibly through augmentation of immune functions.
Keywords	Lactobacillus plantarum ; Immune function ; Wisconsin Upper Respiratory Symptom Survey ; Upper respiratory tract infections ; Stress ; Nutrition. Foods and food supply ; TX341-641 ; Medicine ; R
Subject code	150
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Cambridge University Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Recombinant Mycobacterium bovis bacillus Calmette–Guérin expressing Ag85B-IL-7 fusion protein enhances IL-17A-producing innate γδ T cells

Hatano, Shinya / Goro Matsuzaki / Masayuki Umemura / Naoya Ohara / Toshiki Tamura / Yasunobu Yoshikai

Vaccine. 2016 May 11, v. 34, no. 22

2016

Abstract: Interleukin 7 (IL-7) has an important function in the development and maintenance of IL-17A+ γδ T cells. We here constructed a recombinant Mycobacterium bovis bacillus Calmette–Guérin expressing antigen 85B (Ag85B)-IL-7 fusion protein (rBCG-Ag85B-IL-7). ... ...

Abstract	Interleukin 7 (IL-7) has an important function in the development and maintenance of IL-17A+ γδ T cells. We here constructed a recombinant Mycobacterium bovis bacillus Calmette–Guérin expressing antigen 85B (Ag85B)-IL-7 fusion protein (rBCG-Ag85B-IL-7). The Ag85B-IL-7 fusion protein and IL-7 were detected in the bacterial lysate of rBCG-Ag85B-IL-7. rBCG-Ag85B-IL-7 was the same in number as control rBCG expressing Ag85B (rBCG-Ag85B) in the lung at the early stage after intravenous inoculation, whereas the numbers of IL-17A+ γδ T cells and Ag-specific Th1 cells were significantly higher in the lungs of mice inoculated with rBCG-Ag85B-IL-7 than those inoculated with rBCG-Ag85B. The Ag-specific Th1 cell response was impaired in mice lacking IL-17A+ γδ T cells after inoculation with rBCG-Ag85B-IL-7. Thus, rBCG-Ag85B-IL-7 increases the pool size of IL-17A+ γδ T cells, which subsequently augment the Th1 response to mycobacterial infection.
Keywords	antigens ; interleukin-7 ; intravenous injection ; lungs ; mice ; mycobacterial diseases ; Mycobacterium bovis ; T-lymphocytes ; vaccines
Language	English
Dates of publication	2016-0511
Size	p. 2490-2495.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2016.03.096
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury

Yuki Sato / Akiko Oguchi / Yuji Fukushima / Kyoko Masuda / Naoya Toriu / Keisuke Taniguchi / Takahisa Yoshikawa / Xiaotong Cui / Makiko Kondo / Takeshi Hosoi / Shota Komidori / Yoko Shimizu / Harumi Fujita / Li Jiang / Yingyi Kong / Takashi Yamanashi / Jun Seita / Takuya Yamamoto / Shinya Toyokuni /

Yoko Hamazaki / Masakazu Hattori / Yasunobu Yoshikai / Peter Boor / Jürgen Floege / Hiroshi Kawamoto / Yasuhiro Murakawa / Nagahiro Minato / Motoko Yanagita

The Journal of Clinical Investigation, Vol 132, Iss

2022 Volume 2

Abstract: Tertiary lymphoid tissues (TLTs) facilitate local T and B cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here, we identified TNF superfamily CD153/CD30 signaling ... ...

Abstract	Tertiary lymphoid tissues (TLTs) facilitate local T and B cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here, we identified TNF superfamily CD153/CD30 signaling between 2 unique age-dependent lymphocyte subpopulations, CD153+PD-1+CD4+ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL-21 and IFN-γ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or CD30 deficiency impaired functional SAT cell induction, which resulted in reduced ABC numbers and attenuated TLT formation with improved inflammation, fibrosis, and renal function. Attenuated TLT formation after transplantation of CD153-deficient bone marrow further supported the importance of CD153 in immune cells. Clonal analysis revealed that SAT cells and ABCs in the kidneys arose from both local differentiation and recruitment from the spleen. In the synovium of aged rheumatoid arthritis patients, T peripheral helper/T follicular helper cells and ABCs also expressed CD153 and CD30, respectively. Together, our data reveal a previously unappreciated function of CD153/CD30 signaling in TLT formation and propose targeting the CD153/CD30 signaling pathway as a therapeutic target for slowing kidney disease progression.
Keywords	Inflammation ; Nephrology ; Medicine ; R
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	American Society for Clinical Investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Fas/FasL signaling is critical for the survival of exhausted antigen-specific CD8+ T cells during tumor immune response

Yajima, Toshiki / Akira Mogi / Ei Yamaki / Hiroyuki Kuwano / Ken Shirabe / Kouki Hoshino / Ryo Muranushi / Ryoichi Onozato / Shigebumi Tanaka / Takayuki Kosaka / Yasunobu Yoshikai

Molecular immunology. 2019 Mar., v. 107

2019

Abstract: Antigen (Ag)-specific activated CD8+ T cells are critical for tumor elimination but become exhausted, and thus, dysfunctional during immune response against the tumor due to chronic antigen stimulation. The signaling of immune checkpoint receptors is ... ...

Abstract	Antigen (Ag)-specific activated CD8+ T cells are critical for tumor elimination but become exhausted, and thus, dysfunctional during immune response against the tumor due to chronic antigen stimulation. The signaling of immune checkpoint receptors is known to be a critical component in this exhaustion; however, the fate of these exhausted CD8+ T cells remains unclear. Therefore, to elucidate this, we followed the fate of Ag-specific CD8+ T cells by directly visualizing them using MHC class I tetramers coupled with ovoalubumin257–264 in C57BL/6 mice inoculated with EG.7. We found that the number of generated Ag-specific activated CD8+ T cells decreased via apoptosis during a prolonged tumor immune response. However, the number of Ag-specific CD8+ T cells was significantly higher in Fas ligand (FasL)-dysfunctional gld mice than in control mice, resulting in suppressed tumor growth. In contrast, the enforced expression of Bcl-2 failed to rescue apoptosis of the exhausted CD8+ T cells following EG.7 inoculation. These results suggest that Fas/FasL signaling is critical for the survival of exhausted CD8+ T cells during the tumor immune response.
Keywords	antigens ; apoptosis ; CD8-positive T-lymphocytes ; immune response ; ligands ; major histocompatibility complex ; mice ; neoplasms ; receptors
Language	English
Dates of publication	2019-03
Size	p. 97-105.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2019.01.014
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches

Kazufumi Kunimura / Daiji Sakata / Xin Tun / Takehito Uruno / Miho Ushijima / Tomoya Katakai / Akira Shiraishi / Ryosuke Aihara / Yasuhisa Kamikaseda / Keisuke Matsubara / Hirokazu Kanegane / Shinichiro Sawa / Gérard Eberl / Shouichi Ohga / Yasunobu Yoshikai / Yoshinori Fukui

Cell Reports, Vol 29, Iss 9, Pp 2823-2834.e

2019 Volume 7

Abstract: Summary: Intestinal microfold cells (M cells) in Peyer’s patches are a special subset of epithelial cells that initiate mucosal immune responses through uptake of luminal antigens. Although the cytokine receptor activator of nuclear factor-κB ligand ( ... ...

Abstract	Summary: Intestinal microfold cells (M cells) in Peyer’s patches are a special subset of epithelial cells that initiate mucosal immune responses through uptake of luminal antigens. Although the cytokine receptor activator of nuclear factor-κB ligand (RANKL) expressed on mesenchymal cells triggers differentiation into M cells, other environmental cues remain unknown. Here, we show that the metastasis-promoting protein S100A4 is required for development of mature M cells. S100A4-producing cells are a heterogenous cell population including lysozyme-expressing dendritic cells and group 3 innate lymphoid cells. We found that in the absence of DOCK8, a Cdc42 activator critical for interstitial leukocyte migration, S100A4-producing cells are reduced in the subepithelial dome, resulting in a maturation defect of M cells. While S100A4 promotes differentiation into mature M cells in organoid culture, genetic inactivation of S100a4 prevents the development of mature M cells in mice. Thus, S100A4 is a key environmental cue that regulates M cell differentiation in collaboration with RANKL. : Kunimura et al. find that in the absence of DOCK8, S100A4-producing cells are reduced in the subepithelial dome, resulting in a maturation defect of M cells in Peyer’s patches. In vitro and in vivo studies demonstrate that S100A4 protein is a key environmental factor that promotes M cell maturation. Keywords: intestinal immunity, Peyer's patch, M cell maturation, DOCK8, S100A4-producing cells
Keywords	Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2019-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Oral Administration of Bovine Milk from Cows Hyperimmunized with Intestinal Bacterin Stimulates Lamina Propria T Lymphocytes to Produce Th1-Biased Cytokines in Mice

Yuanyuan Wang / Lianjie Lin / Chunming Yin / Satoru Othtani / Katsuhiko Aoyama / Changlong Lu / Xun Sun / Yasunobu Yoshikai

International Journal of Molecular Sciences, Vol 15, Iss 4, Pp 5458-

2014 Volume 5471

Abstract: The goal of this study was to examine the effects of oral administration of bovine milk from cows hyperimmunized with a proprietary bacterin (immune milk “Sustaina”) on mucosal immunity in the intestine of adult mice. C57BL/6 mice were orally given ... ...

Abstract	The goal of this study was to examine the effects of oral administration of bovine milk from cows hyperimmunized with a proprietary bacterin (immune milk “Sustaina”) on mucosal immunity in the intestine of adult mice. C57BL/6 mice were orally given immune or control milk for two weeks, and then lymphocyte population and the cytokine production in lamina propria of colon in normal mice and mice induced colitis by dextran sulphate sodium (DSS) were detected. We found that the levels of IFN-γ and IL-10 increased, but the levels of IL-17A and IL-4, decreased in lamina propria of colon in immune milk-fed mice as compared with those in control milk-fed mice. Interestingly, oral administration of immune milk partially improved the acute colitis induced by DSS. The levels of TNF-α and IFN-γ increased, but IL-6, IL-17A and IL-4 decreased in lamina propria (LP) of colon in immune milk-fed mice with DSS-induced colitis. Our results suggest that immune milk may stimulate CD4+ T cells to polarize towards a Th1 type response, but contrarily suppress Th17 and Th2 cells responses in large intestinal LP of mice. The results indicate that this kind of immune milk has is able to promote the maintainance of intestinal homeostasis and enhance protection against infection, and could alleviate the symptoms of acute colitis in mice.
Keywords	hyperimmune bovine milk ; intestine ; Th cell response ; dextran sulphate sodium ; colitis ; Chemistry ; QD1-999 ; Science ; Q
Subject code	570
Language	English
Publishing date	2014-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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