Journal ArticleDOI
Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells
Hiroyuki Tezuka,Yukiko Abe,Makoto Iwata,Hajime Takeuchi,Hiromichi Ishikawa,Masayuki Matsushita,Tetsuo Shiohara,Shizuo Akira,Toshiaki Ohteki +8 more
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TLDR
It is shown that IgA class-switch recombination (CSR) is impaired in inducible-nitric-oxide-synthase-deficient (iNOS-/-; gene also called Nos2) mice, and the presence of a naturally occurring TNF-α/iNos-producing dendritic-cell subset may explain the predominance of IgA production in the MALT, critical for gut homeostasis.Abstract:
Immunoglobulin-A has an irreplaceable role in the mucosal defence against infectious microbes. In human and mouse, IgA-producing plasma cells comprise approximately 20% of total plasma cells of peripheral lymphoid tissues, whereas more than 80% of plasma cells produce IgA in mucosa-associated lymphoid tissues (MALT). One of the most biologically important and long-standing questions in immunology is why this 'biased' IgA synthesis takes place in the MALT but not other lymphoid organs. Here we show that IgA class-switch recombination (CSR) is impaired in inducible-nitric-oxide-synthase-deficient (iNOS-/-; gene also called Nos2) mice. iNOS regulates the T-cell-dependent IgA CSR through expression of transforming growth factor-beta receptor, and the T-cell-independent IgA CSR through production of a proliferation-inducing ligand (APRIL, also called Tnfsf13) and a B-cell-activating factor of the tumour necrosis factor (TNF) family (BAFF, also called Tnfsf13b). Notably, iNOS is preferentially expressed in MALT dendritic cells in response to the recognition of commensal bacteria by toll-like receptor. Furthermore, adoptive transfer of iNOS+ dendritic cells rescues IgA production in iNOS-/- mice. Further analysis revealed that the MALT dendritic cells are a TNF-alpha/iNOS-producing dendritic-cell subset, originally identified in mice infected with Listeria monocytogenes. The presence of a naturally occurring TNF-alpha/iNOS-producing dendritic-cell subset may explain the predominance of IgA production in the MALT, critical for gut homeostasis.read more
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The gut microbiota shapes intestinal immune responses during health and disease
TL;DR: Findings indicating that developmental aspects of the adaptive immune system are influenced by bacterial colonization of the gut are discussed, and the possibility that the mammalian immune system, which seems to be designed to control microorganisms, is in fact controlled by microorganisms is raised.
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Taking dendritic cells into medicine
TL;DR: Some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy are presented.
Journal ArticleDOI
Role of the gut microbiota in immunity and inflammatory disease
TL;DR: Understanding the interaction of the microbiota with pathogens and the host might provide new insights into the pathogenesis of disease, as well as novel avenues for preventing and treating intestinal and systemic disorders.
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Vitamin effects on the immune system: vitamins A and D take centre stage
TL;DR: The current understanding of the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation and proliferation, T-helper-cell differentiation, tissue-specific lymphocyte homing, and the production of specific antibody isotypes and regulation of the immune response are presented.
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Monocyte-Mediated Defense Against Microbial Pathogens
TL;DR: In humans and mice, monocytes are divided into two major subsets that either specifically traffic into inflamed tissues or, in the absence of overt inflammation, constitutively maintain tissue macrophage/DC populations.
References
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Journal ArticleDOI
Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Seth Rakoff-Nahoum,Justin C. Paglino,Fatima Eslami-Varzaneh,Stephen C. Edberg,Ruslan Medzhitov +4 more
TL;DR: It is shown that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis and protection from injury.
Journal ArticleDOI
Class Switch Recombination and Hypermutation Require Activation-Induced Cytidine Deaminase (AID), a Potential RNA Editing Enzyme
Masamichi Muramatsu,Kazuo Kinoshita,Sidonia Fagarasan,Shuichi Yamada,Yoichi Shinkai,Tasuku Honjo +5 more
TL;DR: Results suggest that AID may be involved in regulation or catalysis of the DNA modification step of both class switching and somatic hypermutation in CH12F3-2 B lymphoma.
Journal ArticleDOI
Nitric oxide and the immune response
TL;DR: Its striking inter- and intracellular signaling capacity makes it extremely difficult to predict the effect of NOS inhibitors and NO donors, which still hampers therapeutic applications.
Journal ArticleDOI
Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria.
Maria Rescigno,Matteo Urbano,Barbara Valzasina,Maura Francolini,Gianluca Rotta,Roberto Bonasio,Francesca Granucci,Jean Pierre Kraehenbuhl,Paola Ricciardi-Castagnoli +8 more
TL;DR: A new mechanism for bacterial uptake in the mucosa tissues that is mediated by dendritic cells (DCs) is reported, which open the tight junctions between epithelial cells, send dendrites outside the epithelium and directly sample bacteria.
Journal ArticleDOI
Targeted Disruption of the MyD88 Gene Results in Loss of IL-1- and IL-18-Mediated Function
Osamu Adachi,Taro Kawai,Kiyoshi Takeda,Makoto Matsumoto,Hiroko Tsutsui,Masafumi Sakagami,Kenji Nakanishi,Shizuo Akira +7 more
TL;DR: It is demonstrated that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor, and increases in interferon-gamma production and natural killer cell activity in response to IL- 18 are abrogated.
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