自然に発生するTNF/iNOSを生成するデンドリート細胞によるIgA生成の調節
Hiroyuki Tezuka1, Yukiko Abe, Makoto Iwata
1Department of Immunology, Akita University Graduate School of Medicine, Akita 010-8543, Japan.
Nature
|August 24, 2007
まとめ
誘導性酸化窒素合成酵素 (iNOS) は,腸内のIgA生成に不可欠です. この酵素は,免疫細胞のIgAクラススイッチ再結合を調節し,腸が他の組織よりもIgAを多く生成する理由を説明します.
科学分野:
- 免疫学 免疫学とは
- 微生物学 微生物学とは
- 細胞生物学 細胞生物学
背景:
- 免疫グロブリンA (IgA) は,病原体に対する粘膜免疫に不可欠です.
- 他のリンパ性臓器と比較して,粘膜関連リンパ性組織 (MALT) でのIgA生成に重大なバイアスが存在します.
研究 の 目的:
- MALTにおける好ましいIgA合成の基礎となる分子メカニズムを調査する.
- 誘導性酸化窒素合成酵素 (iNOS) がIgAクラススイッチ再結合 (CSR) で果たす役割を特定する.
主な方法:
- イノス欠乏症 (iNOS-/-) のマウスを用いて,IgA CSR.を研究した.
- 分析されたT細胞依存性およびT細胞独立性IgA CSR経路.
- MALTデンドリット細胞の役割と,その相互作用を,トール型受容体経由で共生細菌と研究した.
主要な成果:
- イノス/-マウスでは,IgA CSRが低下していた.
- iNOSは,成長因子ベータ受容体 (T細胞依存) を変容させ,増殖誘発リガンド (APRIL) とB細胞活性化因子 (BAFF) (T細胞依存) を生成することによって,IgA CSRを調節する.
- iNOSは,共生細菌の認識時にMALTの dendritic細胞で発現し,これらの細胞は iNOS-/-マウスでIgAの生産を救出することができます.
結論:
- MALT dendritic 細胞の iNOS は,腸内のバイアス IgA 産生に不可欠です.
- MALTにおけるTNF-alpha/iNOSを生成するデンドリート細胞サブセットは,IgA生成を通じて腸内ホメオスタシスを維持する上で重要な役割を果たします.
関連する概念動画
TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Inflammatory Response
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
T Cell Types and Functions
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...
Inflammatory Bowel Disease II: Ulcerative Colitis
Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...
Inflammatory Bowel Disease III: Crohn's Disease
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...


