炎症性腸疾患におけるヒト大腸メゼンキムの構造的改造
James Kinchen1, Hannah H Chen1, Kaushal Parikh1
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK; Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK.
Cell
|October 2, 2018
まとめ
コロンのメゼンキマ細胞は驚くべき多様性を示し,特定のサブセットが上皮幹細胞をサポートしています. 大腸炎では,これらの細胞は不調になり,炎症性腸疾患 (IBD) の炎症と障壁機能障害を促進します.
科学分野:
- 胃腸内科
- 細胞生物学
- 免疫学
背景:
- 腸内メゼンキマ細胞は腸の健康に不可欠であり,上皮の恒常性,マトリックス再構成,免疫,炎症に影響を与えます.
- 腸内メゼンキマ細胞の異質性と特定の役割は,特に上皮幹細胞と炎症状態に関連して,ほとんど研究されていない.
研究 の 目的:
- 単細胞プロファイリングを使用して大腸内メゼンキーム内の細胞異質性を定義する.
- 腸内皮質幹細胞の機能維持に関与する特定のメゼンキマ細胞のサブセットを特定する.
- 大腸炎と炎症性腸疾患 (IBD) の文脈における大腸内膜細胞の役割を調査する.
主な方法:
- 16500以上の大腸内メゼンキマ細胞の偏らない単細胞RNAシーケンシング.
- 異なった線維細胞のサブセット,ペリサイト,およびミオフィブラストを識別するための転写プロファイリング.
- 大腸炎の際の表皮機能と疾患の重度に対するメゼンキマ細胞集団の影響を評価するインビボ試験.
主要な成果:
- 4つの異なる線維芽細胞のサブセット,ペリサイト,およびミオフィブロブラストが結腸内メゼンキーム内で特定されました.
- SOX6,F3 (CD142) およびWNT遺伝子を発現する特定のメゼンキーマニッチ集団は,大腸の上皮幹細胞機能に不可欠であることが判明した.
- 大腸炎は,このニッチの調節不全を誘発し,TNFSF14,IL-33,およびリシル酸化物を発現する活性化メゼンキマ群を促進し,上皮の増殖を阻害し,疾患の重症性を悪化させた.
結論:
- 大腸内メゼンキームは細胞の異質性を有しており,異なるサブセットが特殊な役割を担っている.
- SOX6-F3-WNTを発現するメゼンキマのニッチは,大腸上皮幹細胞の機能を維持するために不可欠です.
- 大腸炎中のメゼンキマ細胞の活性化は,IBDにおける炎症,バリア機能障害,および疾患の重症化に寄与する.
関連する概念動画
01:30Inflammatory Bowel Disease II: Crohn's Disease
541
Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
541
01:21Inflammatory Bowel Disease V: Surgical Management
281
Surgical interventions for inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, are essential in managing symptoms and addressing complications. The selection of surgical procedures is contingent upon the specific conditions and complications that stem from these illnesses.
Here are some common surgical interventions for IBD:
Here are some common surgical interventions for IBD:
281
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
510
Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
510
01:17Chronic Bowel Disorders: Introduction
602
Chronic bowel diseases are a group of long-term conditions affecting the digestive tract, characterized by inflammation and damage to the gut lining. These conditions primarily include irritable bowel syndrome and inflammatory bowel disease.
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
602
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
476
Various diagnostic tests are employed in the diagnostic process for Inflammatory Bowel Disease (IBD), particularly to differentiate between Crohn's disease and ulcerative colitis.
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
476
01:23Renewal of Intestinal Stem Cells
2.9K
The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
2.9K