HEИндивидуална стипендия2023–2025

TANK_Sepsis · Targeting Amino acid uptake into NK cells to limit pathogenesis in sepsis

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

Период: 2023-10-01 → 2025-09-30
Финансиране от ЕС: 215 534 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

NK клетките и начинът, по който те усвояват аминокиселини при сепсис, се анализират чрез модели с мишки. Това помага за разработването на нови стратегии за контролиране на опасната възпалителна реакция на имунната система.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Targeting Amino acid uptake into NK cells to limit pathogenesis in sepsis

Sepsis is a life-threatening condition where the immune system first becomes dangerously overactive, followed by prolonged immunosuppression. One of the key players in this process are natural killer (NK) cells, immune cells that help fight infection but can also worsen inflammation if they become too active. In the era of antimicrobial resistance, it is important to develop therapies that target over- or under-activated immune cells to balance and promote the natural immune response to the infection. However, currently there is a limited number of these therapies. This project set out to understand how NK cells use nutrients—especially amino acids, the building blocks of proteins—when the body is fighting severe infection. The aim was to discover whether changes in nutrient availability could be used to control NK-cell activity and create new strategies to reduce harmful inflammation in sepsis. The main objectives of the project were: 1. Investigate the dynamics of NK cell response in mouse models of sepsis 2. Test the importance of amino acid transporters Slc1a5 and Slc7a5 for NK cell function in sepsis using genetically modified mice 3. Test potential therapies altering amino acid availability for NK cells in sepsis

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

Цел на проекта

Sepsis is a global health challenge, accounting for around 20% of deaths worldwide. While sepsis is induced by uncontrolled dissemination of infection, significant contribution to disease pathogenesis is made by overwhelming production of proinflammatory mediators, a so-called “cytokine storm”. There is a pressing need for new target therapies to dampen this immunopathogenesis while still allowing bacterial clearance. Although Natural Killer (NK) cells are vital for host innate responses, they are important contributors to the tissue damage during bacterial sepsis, in particular, via production of excessive amounts of IFNg. Therefore, dampening NK cell IFNg production represents a promising tool for sepsis treatment. Recent studies from the host institution have shown that metabolic processes are essential for NK cell functions. In particular, certain amino acid transporters are key to support IFNg expression by NK cells. I thus hypothesize that limiting amino acid supply to NK cells will restrict production of IFNg, dampen the cytokine storm, and improve the course of bacterial sepsis. To prove this idea, I will combine my experience in mouse models of septic shock with host institution’s background on immunometabolism and bacterial infections. First, I will employ a powerful “metabolic toolbox” established at the supervisor’s lab to characterize metabolic phenotype of NK cells in bacterial sepsis. Next, I will use mice with genetic ablation of key amino acid transporters specifically in NK cells to study their role in “cytokine storm” during sepsis. Finally, I will test pharmacological compounds, able to limit amino acid availability, for their potential to prevent excessive inflammation during sepsis. At the end of the project, I will acquire key professional skills, including “metabolic toolbox” and bacterial infection model, that will benefit my further career, as well as characterize new potential therapeutic opportunity for treatment of sepsis.

Оригинален текст от CORDIS (на английски).

Участници

THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN · DublinКоординаторИрландия