miRNAs in TH2 cells · Role of extracellular miRNAs in T cell development, TH2 cell differentiation and TH2 cell-mediated effector function
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2015-08-01 → 2017-07-31
- Финансиране от ЕС
- 183 455 €
- Участници
- 2
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Специфични молекули, наречени miRNA, които се отделят от Т-хелпер 2 клетките, се изследват за влиянието им върху алергичната астма. Разбирането на тези механизми помага за търсенето на нови начини за предотвратяване на алергиите.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Role of extracellular miRNAs in T cell development, TH2 cell differentiation and TH2 cell-mediated effector function
Millions of Europeans suffer from allergy, a condition worryingly common among children and young adults. Although mostly manageable, some allergies can be life threatening. Standard of care is limited to the management of symptoms, and therapies aimed at curing the disease are currently absent . Allergic reactions are caused by a hyper-activated immune system. Immune cells in the body, called “T helper 2” (TH2) cells, are the coordinators of an inflammatory cascade that is responsible for many of the pathologies and symptoms associated with allergy. The aim of this project is to better understand how TH2 cells develop and cause disease, to identify novel therapies to prevent allergy. TH2 cells secrete soluble protein mediators called “cytokines” that pull the trigger on inflammation. For example, factors secreted by TH2 cells are responsible for sensitisation to allergens like pollen, grass or house dust mite. These factors are linked to sneezing, wheezing and rashes typical of allergic reactions. They also cause hyper-secretion of mucus in the airways, particularly in allergic asthma. This project investigates a new class of secreted factors - called miRNAs - produced by TH2 cells. While this project was supported by the European Commission, we performed experiments to identify: i) which miRNAs are secreted by TH2 cells; ii) which miRNAs are transferred to other cells of the immune system; iii) what are the molecular mechanism that govern miRNA secretion; iv) what is the biological implication of secreted miRNAs in the development of allergic asthma. As a result of this project we will publish our findings in full advancing our understanding of how the body responds to allergens, the immune system and the development of immunological diseases (see below). This project will help to expand the therapeutic window to treat different immunological disorders, from allergies to autoimmune diseases.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
It is estimated that more than 200 million Europeans suffer from at least one type of allergy. This condition is elicited by an hyper-activated type-2 inflammatory response coordinated by T helper (TH)-2 cells. In spite a good insight into the molecular mechanisms that triggers TH2 cells activation, the lack in understanding their post-transcriptional regulation is hampering the access to new potential therapeutic targets to curtail the allergy epidemic.Micro-RNA (miRNAs) are regulatory molecules essential for life, which play a fundamental role in shaping cellular functions via post-transcriptional repression of the cellular transcriptome. Though previously considered to operate exclusively inside the parent cell, it is now acknowledged that miRNAs can exit cellular boundaries and control transcription in bystander cells. We recently reported that regulatory T (TREG) cells secret specific miRNAs to repress TH1 cell-mediated immunopathology, and ameliorate a mouse model of autoimmune disease.In this proposal, we will address the role of extracellular miRNAs for the normal T cell development and during allergic inflammation of the airways. To this end, we produced a novel animal model that allows - for the first time - to selectively ablate the activity of extracellular miRNAs in T cells. We will use biochemical, RNA-sequencing and bioinformatics analysis to identify the molecular mechanisms for miRNAs sorting to exocytosis and to identify the miRNAs transferred to and from TH2 cells. This proposal will significantly expand our understanding of transferred miRNAs in the contest of health and disease, and will uncover novel cellular pathways to exploit as therapeutic targets.
Оригинален текст от CORDIS (на английски).
Участници
- THE FRANCIS CRICK INSTITUTE LIMITED · LondonКоординаторОбединеното кралство
- UNITED KINGDOM RESEARCH AND INNOVATION · SWINDONОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз