HEИндивидуална стипендия2022–2025

MacTalk · Adipose tissue-Liver Macrophage CrossTalk in NASH and Fibrosis

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

Период: 2022-09-01 → 2025-06-30
Финансиране от ЕС: 204 937 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Имунните клетки в мастната тъкан изпращат сигнали, които влияят върху поведението на макрофагите в черния дроб. Разбирането на този механизъм помага да се разбере как затлъстяването води до възпаление и белези по органите.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Adipose tissue-Liver Macrophage CrossTalk in NASH and Fibrosis

Obesity and its related health complications are among the most pressing health challenges in Europe and worldwide. One major complication is metabolic dysfunction–associated steatotic liver disease (MASLD), which affects approximately 25% of the population. MASLD can progress from simple fat accumulation in the liver to chronic liver inflammation and scarring (fibrosis), and in severe cases liver failure or liver cancer. Despite this urgent clinical problem, current treatment options are limited. A key reason is that we still do not fully understand why and how obesity drives liver disease at the cellular level. Recent findings suggest that immune cells in fat tissue, named adipose tissue macrophages (ATMs), send signals that influence the immune cells, including macrophages, of the liver. In turn, this may determine whether MASLD progresses to more severe disease such as liver fibrosis. However, exactly how ATMs affect liver macrophages, their activation state, and their localization in the liver is unknown. This knowledge gap has limited progress toward targeted therapies. Our project set out with an ambitious goal: to uncover how adipose tissue macrophages shape liver macrophages and thereby drive liver inflammation and fibrosis. We framed this around two core objectives: • Objective 1: Define the impact of adipose tissue macrophages on liver macrophage composition and liver fibrosis in MASLD. • Objective 2: Elucidate how adipose tissue macrophages influence liver macrophage function. Thus, we aimed to pinpoint factors secreted by ATMs that alter macrophage behavior in the liver. By integrating animal models, cell models and a human translational study, together with advanced immunophenotyping, this project aimed to take a comprehensive approach to this complex problem. The innovation of this project lies in connecting two tissues, fat and liver, through their immune systems. Understanding this “crosstalk” could open entirely new avenues for treatment to timely stop disease progression. The impact could be substantial, with the potential to influence clinical strategies for millions of people with obesity-related liver disease. By considering sex differences, the project also ensures its results are relevant for gender equality.

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

Цел на проекта

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and damage. This drives liver inflammation, promoting the progression to non-alcoholic steatohepatitis (NASH) and liver fibrosis. There are currently no approved therapies for NASH and fibrosis, which is in part due to a lack of knowledge of the immunological events underpinning NASH and fibrosis. The pathogenesis of NASH is strongly influenced by crosstalk with other tissues. There is increasing evidence that specifically obese adipose tissue macrophages (ATMs) are directly linked to liver pathology. In this respect, the host lab has shown that obese ATMs increase hepatic macrophage number. However, the exact changes in macrophage subsets and phenotypes were not investigated. I recently demonstrated that in NASH liver macrophages display large heterogeneity in phenotype and tissue localization and this plays a key role in NASH-associated liver fibrosis. Based on this combined preliminary data generated by the host lab and me, I hypothesize that ATMs alter hepatic macrophage composition and consequently affect the progression of NASH to liver fibrosis. By combining the mouse models and expertise available in the host lab and advanced technology present at the host institute, with my expertise in detailed immunophenotyping of the liver in NASH and fibrosis, I will address this innovative hypothesis in great detail. To bridge the translational gap from animal studies, I will investigate the potential contribution of ATMs to hepatic inflammation and fibrosis in humans by using unique fresh paired adipose tissue and liver biopsies available through the clinical network of the host lab. MacTalk integrates the scientific and technical expertise of both me and the host lab, creating a unique framework to identify novel mediators of hepatic inflammation and fibrosis. Furthermore, MacTalk will lay a strong foundation for my future career as independent researcher in the field of liver fibrosis.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITEIT MAASTRICHT · MaastrichtКоординаторНидерландия