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Article ; Online: Decoding Toll-like receptors: Recent insights and perspectives in innate immunity.

Kawai, Taro / Ikegawa, Moe / Ori, Daisuke / Akira, Shizuo

2024 Volume 57, Issue 4, Page(s) 649–673

Abstract: Toll-like receptors (TLRs) are an evolutionarily conserved family in the innate immune system and are the first line of host defense against microbial pathogens by recognizing pathogen-associated molecular patterns (PAMPs). TLRs, categorized into cell ... ...

Abstract	Toll-like receptors (TLRs) are an evolutionarily conserved family in the innate immune system and are the first line of host defense against microbial pathogens by recognizing pathogen-associated molecular patterns (PAMPs). TLRs, categorized into cell surface and endosomal subfamilies, recognize diverse PAMPs, and structural elucidation of TLRs and PAMP complexes has revealed their intricate mechanisms. TLRs activate common and specific signaling pathways to shape immune responses. Recent studies have shown the importance of post-transcriptional regulation in TLR-mediated inflammatory responses. Despite their protective functions, aberrant responses of TLRs contribute to inflammatory and autoimmune disorders. Understanding the delicate balance between TLR activation and regulatory mechanisms is crucial for deciphering their dual role in immune defense and disease pathogenesis. This review provides an overview of recent insights into the history of TLR discovery, elucidation of TLR ligands and signaling pathways, and their relevance to various diseases.
MeSH term(s)	Pathogen-Associated Molecular Pattern Molecules ; Toll-Like Receptors/metabolism ; Immunity, Innate/physiology ; Signal Transduction ; Gene Expression Regulation
Chemical Substances	Pathogen-Associated Molecular Pattern Molecules ; Toll-Like Receptors
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2024.03.004
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 69: Show issues

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Article ; Online: Pathophysiological functions of self-derived DNA.

Ori, Daisuke / Kawai, Taro

International reviews of immunology

2022 Volume 42, Issue 4, Page(s) 274–286

Abstract: Inflammation plays indispensable roles in building the immune responses such as acquired immunity against harmful pathogens. Furthermore, it is essential for maintaining biological homeostasis in ever-changing conditions. Pattern-recognition receptors ( ... ...

Abstract	Inflammation plays indispensable roles in building the immune responses such as acquired immunity against harmful pathogens. Furthermore, it is essential for maintaining biological homeostasis in ever-changing conditions. Pattern-recognition receptors (PRRs) reside in cell membranes, endosomes or cytoplasm, and function as triggers for inflammatory responses. Binding of pathogen- or self-derived components, such as DNA, to PRRs activates downstream signaling cascades, resulting in the production of a series of pro-inflammatory cytokines and type I interferons (IFNs). While these series of responses are essential for host defense, the unexpected release of DNA from the nucleus or mitochondria of host cells can lead to autoimmune and autoinflammatory diseases. In this review, we focus on DNA-sensing mechanisms
MeSH term(s)	Humans ; Immunity, Innate ; Receptors, Pattern Recognition/metabolism ; Cytokines/metabolism ; Adaptive Immunity ; DNA/genetics
Chemical Substances	Receptors, Pattern Recognition ; Cytokines ; DNA (9007-49-2)
Language	English
Publishing date	2022-05-02
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632825-8
ISSN	1563-5244 ; 1545-5858 ; 0883-0185
ISSN (online)	1563-5244 ; 1545-5858
ISSN	0883-0185
DOI	10.1080/08830185.2022.2070616
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Zs.A 2156: Show issues

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Article ; Online: Identification and characterization of putative enhancer regions that direct Il6 transcription in murine macrophages.

Kano, Norisuke / Miki, Takeo / Uehara, Yurina / Ori, Daisuke / Kawai, Taro

International immunology

2024

Abstract: Interleukin-6 (IL-6) plays a crucial role in various cellular functions, including the innate and adaptive immune responses. Dysregulated expression of IL-6 is associated with hyperinflammation and chronic inflammatory diseases. In this study, we aimed ... ...

Abstract	Interleukin-6 (IL-6) plays a crucial role in various cellular functions, including the innate and adaptive immune responses. Dysregulated expression of IL-6 is associated with hyperinflammation and chronic inflammatory diseases. In this study, we aimed to identify the enhancer regions responsible for robust Il6 mRNA expression in murine macrophages. Through comprehensive genome-wide ChIP-seq and ATAC-seq analyses, we identified two distinct clusters, termed E1 and E2 regions, located at -144 kb to -163 kb relative to the Il6 transcription start site in lipopolysaccharide (LPS)-activated murine macrophages. These clusters exhibited an accumulation of histone modification marks (H3K27ac and H3K4me1), as well as open chromatin, and were found to contain binding sites for the transcription factors PU.1, NF-κB, C/EBPβ, and JunB. Upregulation of non-coding RNA (ncRNA) transcripts from the E1 and E2 regions was observed upon LPS stimulation, and repression of these ncRNAs resulted in abrogation of Il6 expression. Additionally, deletion of either E1 or E2 regions significantly impaired Il6 expression, while CRISPR/dCas9 activation-mediated recruitment of the co-activator p300 to the E1 and E2 regions facilitated Il6 expression. Collectively, our findings suggest that the E1 and E2 regions serve as putative enhancers for Il6 expression.
Language	English
Publishing date	2024-04-22
Publishing country	England
Document type	Journal Article
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxae024
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Zs.A 2619: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Generating an organ-deficient animal model using a multi-targeted CRISPR-Cas9 system.

Lim, Jonathan Jun-Yong / Murata, Yamato / Yuri, Shunsuke / Kitamuro, Kohei / Kawai, Taro / Isotani, Ayako

Scientific reports

2024 Volume 14, Issue 1, Page(s) 10636

Abstract: Gene-knockout animal models with organ-deficient phenotypes used for blastocyst complementation are generally not viable. Animals need to be maintained as heterozygous mutants, and homozygous mutant embryos yield only one-fourth of all embryos. In this ... ...

Abstract	Gene-knockout animal models with organ-deficient phenotypes used for blastocyst complementation are generally not viable. Animals need to be maintained as heterozygous mutants, and homozygous mutant embryos yield only one-fourth of all embryos. In this study, we generated organ-deficient embryos using the CRISPR-Cas9-sgRNA
MeSH term(s)	Animals ; CRISPR-Cas Systems ; Mice ; Rats ; RNA, Guide, CRISPR-Cas Systems/genetics ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Thymus Gland/metabolism ; Models, Animal ; Blastocyst/metabolism
Chemical Substances	RNA, Guide, CRISPR-Cas Systems ; Whn protein ; Forkhead Transcription Factors
Language	English
Publishing date	2024-05-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-61167-3
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Article ; Online: Antigen Presentation in the Lung.

Kawasaki, Takumi / Ikegawa, Moe / Kawai, Taro

Frontiers in immunology

2022 Volume 13, Page(s) 860915

Abstract: The lungs are constantly exposed to environmental and infectious agents such as dust, viruses, fungi, and bacteria that invade the lungs upon breathing. The lungs are equipped with an immune defense mechanism that involves a wide variety of immunological ...

Abstract	The lungs are constantly exposed to environmental and infectious agents such as dust, viruses, fungi, and bacteria that invade the lungs upon breathing. The lungs are equipped with an immune defense mechanism that involves a wide variety of immunological cells to eliminate these agents. Various types of dendritic cells (DCs) and macrophages (MACs) function as professional antigen-presenting cells (APCs) that engulf pathogens through endocytosis or phagocytosis and degrade proteins derived from them into peptide fragments. During this process, DCs and MACs present the peptides on their major histocompatibility complex class I (MHC-I) or MHC-II protein complex to naïve CD8
MeSH term(s)	Antigen Presentation ; Cells, Cultured ; Dendritic Cells ; Endothelial Cells ; Lung
Language	English
Publishing date	2022-05-09
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.860915
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Article ; Online: Penaeus monodon

Soponpong, Suthinee / Amparyup, Piti / Kawai, Taro / Tassanakajon, Anchalee

Frontiers in immunology

2022 Volume 12, Page(s) 818267

Abstract: Interferon regulatory factors (IRFs) are transcription factors found in both vertebrates and invertebrates that were recently identified and found to play an important role in antiviral immunity in black tiger ... ...

Abstract	Interferon regulatory factors (IRFs) are transcription factors found in both vertebrates and invertebrates that were recently identified and found to play an important role in antiviral immunity in black tiger shrimp
MeSH term(s)	Animals ; Antimicrobial Peptides/genetics ; Antimicrobial Peptides/metabolism ; Cell Line ; Cells, Cultured ; DNA/immunology ; Gene Expression Regulation ; Gene Silencing ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Interferon Regulatory Factors/metabolism ; Interferon Regulatory Factors/pharmacology ; Interferons/genetics ; Interferons/metabolism ; Membrane Proteins/metabolism ; Penaeidae/physiology ; Signal Transduction
Chemical Substances	Antimicrobial Peptides ; Interferon Regulatory Factors ; Membrane Proteins ; DNA (9007-49-2) ; Interferons (9008-11-1)
Language	English
Publishing date	2022-01-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.818267
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Article ; Online: Pathophysiological Role of Nucleic Acid-Sensing Pattern Recognition Receptors in Inflammatory Diseases.

Kano, Norisuke / Ong, Guang Han / Ori, Daisuke / Kawai, Taro

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 910654

Abstract: Pattern recognition receptors (PRRs) play critical roles in recognizing pathogen-derived nucleic acids and inducing innate immune responses, such as inflammation and type I interferon production. PRRs that recognize nucleic acids include members of ... ...

Abstract	Pattern recognition receptors (PRRs) play critical roles in recognizing pathogen-derived nucleic acids and inducing innate immune responses, such as inflammation and type I interferon production. PRRs that recognize nucleic acids include members of endosomal Toll-like receptors, cytosolic retinoic acid inducible gene I-like receptors, cyclic GMP-AMP synthase, absent in melanoma 2-like receptors, and nucleotide binding oligomerization domain-like receptors. Aberrant recognition of self-derived nucleic acids by these PRRs or unexpected activation of downstream signaling pathways results in the constitutive production of type I interferons and inflammatory cytokines, which lead to the development of autoimmune or autoinflammatory diseases. In this review, we focus on the nucleic acid-sensing machinery and its pathophysiological roles in various inflammatory diseases.
MeSH term(s)	Immunity, Innate ; Interferon Type I/metabolism ; Nucleic Acids/metabolism ; Receptors, Pattern Recognition ; Toll-Like Receptors
Chemical Substances	Interferon Type I ; Nucleic Acids ; Receptors, Pattern Recognition ; Toll-Like Receptors
Language	English
Publishing date	2022-06-06
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.910654
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Article ; Online: Inhibition of lipopolysaccharide-induced inflammatory responses by 1'-acetoxychavicol acetate.

Ong, Guang Han / Ori, Daisuke / Kawasaki, Takumi / Kawai, Taro

Genes to cells : devoted to molecular & cellular mechanisms

2022 Volume 27, Issue 7, Page(s) 482–492

Abstract: Lipopolysaccharide on gram negative bacteria can be detected by Toll-like receptor 4 (TLR4) to elicit a series of innate immune responses, leading to inflammation to eliminate the targeted pathogen. However, dysregulation in the responses results in ... ...

Abstract	Lipopolysaccharide on gram negative bacteria can be detected by Toll-like receptor 4 (TLR4) to elicit a series of innate immune responses, leading to inflammation to eliminate the targeted pathogen. However, dysregulation in the responses results in excessive inflammation. The 1'-acetoxychavicol acetate (ACA) is a bioactive compound originated from Alpinia species known to have anti-inflammatory and apoptosis-inducing properties. Here, we found that ACA inhibits lipopolysaccharide-induced expression and production of proinflammatory cytokines such as interleukin 6 and TNFα by macrophages. ACA suppresses the activation of NF-κB and MAP kinases in TLR4 signaling. Moreover, ACA also inhibits TLR4-mediated induction of type I interferon by suppressing IRF3 activation. In lipopolysaccharide-challenged mice, ACA treatment successfully increased the survival of mice and alleviated inflammation in the lung. Thus, ACA is a potential anti-inflammatory agent to regulate excessive inflammation.
MeSH term(s)	Animals ; Benzyl Alcohols/pharmacology ; Cytokines/metabolism ; Inflammation/drug therapy ; Lipopolysaccharides/pharmacology ; Mice ; NF-kappa B/metabolism ; Toll-Like Receptor 4/metabolism
Chemical Substances	Benzyl Alcohols ; Cytokines ; Lipopolysaccharides ; NF-kappa B ; Toll-Like Receptor 4 ; 1'-acetoxychavicol acetate (SQV3080A20)
Language	English
Publishing date	2022-05-08
Publishing country	England
Document type	Journal Article
ZDB-ID	1330000-3
ISSN	1365-2443 ; 1356-9597
ISSN (online)	1365-2443
ISSN	1356-9597
DOI	10.1111/gtc.12943
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Zs.A 4539: Show issues

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Article ; Online: Signaling Through Nucleic Acid Sensors and Their Roles in Inflammatory Diseases.

Okude, Haruna / Ori, Daisuke / Kawai, Taro

Frontiers in immunology

2021 Volume 11, Page(s) 625833

Abstract: Recognition of pathogen-derived nucleic acids by pattern-recognition receptors (PRRs) is essential for eliciting antiviral immune responses by inducing the production of type I interferons (IFNs) and proinflammatory cytokines. Such responses are a ... ...

Abstract	Recognition of pathogen-derived nucleic acids by pattern-recognition receptors (PRRs) is essential for eliciting antiviral immune responses by inducing the production of type I interferons (IFNs) and proinflammatory cytokines. Such responses are a prerequisite for mounting innate and pathogen-specific adaptive immune responses. However, host cells also use nucleic acids as carriers of genetic information, and the aberrant recognition of self-nucleic acids by PRRs is associated with the onset of autoimmune or autoinflammatory diseases. In this review, we describe the mechanisms of nucleic acid sensing by PRRs, including Toll-like receptors, RIG-I-like receptors, and DNA sensor molecules, and their signaling pathways as well as the disorders caused by uncontrolled or unnecessary activation of these PRRs.
MeSH term(s)	Animals ; DNA/immunology ; Humans ; Immunity, Innate ; Inflammation/immunology ; Inflammation/pathology ; Interferon Type I/immunology ; Receptors, Pattern Recognition/immunology ; Signal Transduction/immunology
Chemical Substances	Interferon Type I ; Receptors, Pattern Recognition ; DNA (9007-49-2)
Language	English
Publishing date	2021-01-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.625833
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Article: Discrimination Between Self and Non-Self-Nucleic Acids by the Innate Immune System.

Kawasaki, Takumi / Kawai, Taro

International review of cell and molecular biology

2018 Volume 344, Page(s) 1–30

Abstract: During viral and bacterial infections, the innate immune system recognizes various types of pathogen-associated molecular patterns (PAMPs), such as nucleic acids, via a series of membrane-bound or cytosolic pattern-recognition receptors. These include ... ...

Abstract	During viral and bacterial infections, the innate immune system recognizes various types of pathogen-associated molecular patterns (PAMPs), such as nucleic acids, via a series of membrane-bound or cytosolic pattern-recognition receptors. These include Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), AIM2-like receptors (ALRs), and cytosolic DNA sensors. The binding of PAMPs to these receptors triggers the production of type I interferon (IFN) and inflammatory cytokines. Type I IFN induces the expression of interferon stimulated genes (ISGs), which protect surrounding cells from infection. Some ISGs are nucleic acids-binding proteins that bind viral nucleic acids and suppress their replication. As nucleic acids are essential components that store and transmit genetic information in every species, infectious pathogens have developed systems to escape from the host nucleic acid recognition system. Host cells also have their own nucleic acids that are frequently released to the extracellular milieu or the cytoplasm during cell death or stress responses, which, if able to bind pattern-recognition receptors, would induce autoimmunity and inflammation. Therefore, host cells have acquired mechanisms to protect themselves from contact with their own nucleic acids. In this review, we describe recent research progress into the nucleic acid recognition mechanism and the molecular bases of discrimination between self and non-self-nucleic acids.
MeSH term(s)	Animals ; Autoantigens/metabolism ; DNA/metabolism ; Humans ; Immunity, Innate ; Inflammation/pathology ; Nucleic Acids/metabolism ; RNA/metabolism
Chemical Substances	Autoantigens ; Nucleic Acids ; RNA (63231-63-0) ; DNA (9007-49-2)
Keywords	covid19
Language	English
Publishing date	2018-10-26
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2427220-6
ISSN	1937-6448 ; 0074-7696
ISSN	1937-6448 ; 0074-7696
DOI	10.1016/bs.ircmb.2018.08.004
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