H2020Индивидуална стипендия2015–2017

Tbet ILC JFN · The role of innate lymphoid cells in regulating intestinal inflammation

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2015-05-01 → 2017-10-08
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Вродени лимфоидни клетки (ILCs) в червата се изследват, за да се разбере как някои от тях предизвикват възпаление, например при болестта на Крон. Това помага за разбирането на механизмите зад заболявания като диабет, затлъстяване и рак.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

The role of innate lymphoid cells in regulating intestinal inflammation

The gut is a complex organ, and many aspects of human health depend on proper gut function. There are three main compartments in the gut: (1) the epithelial layer, which forms a barrier, like the skin, against the outside environment; (2) the immune system, which protects the body from infections; and (3) the microorganisms that live in our gut, collectively known as the gut microbiota. Inappropriate interactions between these three compartments can impair gut functioning and affect other organs as well, and such events have been associated with the development of several diseases such as cancer, diabetes, obesity and inflammatory bowel disease (IBD). These diseases constitute a significant public health and economic problem. The aim of this project was to study a specific type of immune cells that are abundant and have important functions in the gut, called innate lymphoid cells (ILCs), and understand their role during intestinal disease. There are different sub-populations of ILCs, some that can protect against gut infections, whereas others can promote intestinal inflammation. For example, Crohn’s Disease patients often accumulate a particular sub-population of ILCs, called ILC1s, in their inflamed gut, suggesting they play a role in causing this disease.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The maintenance of intestinal homeostasis has local and systemic implications for the host health and depends on a balance regulated by interactions between the immune system and the gut microbiota. Recently, it has become clear that a newly identified group of cells, innate lymphoid cells (ILCs), have a crucial role in intestinal homeostasis and host defence. ILCs respond rapidly to changes in the gut microenvironment and produce several cytokines that regulate intestinal inflammation. Although the pathways responsible for ILCs’ development and differentiation are only starting to be elucidated, the transcription factor T-bet has emerged as a key regulator of these processes.This proposal aims to clarify the molecular mechanisms involved in the T-bet-dependent development and function of ILCs and how these processes can be modulated by the intestinal microbiota. First, we propose to use a novel lineage-tracing mouse model that uses dual fluorescence reporters to differentiate between cells that currently express T-bet from cells that used to express T-bet, in order to distinguish between the mechanisms responsible for ILCs development from the mechanisms involved in ILCs function. In addition, we aim to uncover novel T-bet associated pathways that are active on intestinal ILCs, and understand how these pathways are regulated by the gut microbiome. Moreover, we aim to develop a novel in vitro co-culture system of ILCs in intestinal organoids, which will facilitate our studies and benefit future studies investigating the development and functions of intestinal lymphocytes. The detailed study of ILCs development, differentiation and function and the identification of novel T-bet and microbiota associated pathways will open new possibilities in the modulation of ILC’s functions and inform on how to divert these cells away from their pathogenic phenotypes that are responsible for gut inflammation and could have a significant impact on the field of intestinal immunity.

Оригинален текст от CORDIS (на английски).

Участници

KING'S COLLEGE LONDON · LondonКоординаторОбединеното кралство